125,506 results match your criteria Myeloid Proliferations Related to Down Syndrome


Methadone therapy modulate the dendritic cells of heroin addicts.

Int Immunopharmacol 2018 Dec 3;66:330-335. Epub 2018 Dec 3.

Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences, Arak, Iran; Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran. Electronic address:

Evidence from various studies suggests that narcotics abuse may exert adverse immunomodulatory effects on immune responses. The aim of this research was to understand the effects of detoxification with methadone on the percentage of dendritic cells (DCs) and expression of its markers in heroin addicts. In this study, myeloid DCs (CD11c) and plasmacytoid DCs (CD123) were examined in two groups. Read More

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December 2018
2 Reads

Loss of K607 and E877 interaction is a key reason for JAK2 K607N mutation caused acute myeloid leukemia.

Int J Biol Macromol 2018 Dec 3. Epub 2018 Dec 3.

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address:

Oncogenic activation of tyrosine kinase signaling pathway is recurrent in human leukemia. The acquired Janus kinase 2 (JAK2) K607N somatic mutation was detected in about 6.8% of acute myeloid leukemia (AML) patients. Read More

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December 2018
2 Reads
2.858 Impact Factor

Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs).

Biomol Ther (Seoul) 2018 Dec 6. Epub 2018 Dec 6.

Division of Biological Sciences, Research Institute of Women's Health and Cellular Heterogeneity Research Center, Sookmyung Women's University, Seoul 04310, Republic of Korea.

Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Read More

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December 2018
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Loss of ARHGEF1 causes a human primary antibody deficiency.

J Clin Invest 2018 Dec 6. Epub 2018 Dec 6.

ARHGEF1 is a RhoA-specific guanine nucleotide exchange factor expressed in hematopoietic cells. We used whole-exome sequencing to identify compound heterozygous mutations in ARHGEF1, resulting in the loss of ARHGEF1 protein expression in two primary-antibody-deficient siblings presenting with recurrent severe respiratory tract infections and bronchiectasis. Both ARHGEF1-deficient patients showed an abnormal B cell immunophenotype, with a deficiency in marginal-zone and memory B cells and an increased frequency of transitional B cells. Read More

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December 2018

Unexplained cytopenias in an adolescent? You GATA think about it.

J Assoc Genet Technol 2018 ;44(4):135-136

Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT.

Objectives: The GATA family of DNA binding proteins consists of six different transcription factors (GATA1-6), each with a diverse biologic function. The transcription factors GATA1-3 function primarily to orchestrate hematopoiesis; however, they have roles in non-hematopoietic cells as well. Much of our current knowledge of the GATA transcription factors has come through observation of disease states with known GATA mutations. Read More

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January 2018

Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes.

Cancer 2018 Dec 6. Epub 2018 Dec 6.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The revised 2017 European LeukemiaNet (ELN) classification (ELN-2017) of acute myeloid leukemia (AML) divides patients into 3 prognostic risk categories, with additional factors such as the fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) allele ratio (AR) considered for risk stratification. To the best of the authors' knowledge, the prognostic usefulness of ELN-2017 in comparison with ELN-2010 in younger patients with AML has not been validated to date.

Methods: The authors performed a retrospective study on patients aged <60 years who received idarubicin plus cytarabine (IA)-based induction chemotherapy for newly diagnosed AML. Read More

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December 2018

A multicenter study of patients with multisystem Langerhans cell histiocytosis who develop secondary hemophagocytic lymphohistiocytosis.

Cancer 2018 Dec 6. Epub 2018 Dec 6.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a-positive (CD1a )/CD207 histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Read More

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December 2018
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Benzene Exposure Response and Risk of Myeloid Neoplasms in Chinese Workers: A Multicenter Case-Cohort Study.

J Natl Cancer Inst 2018 Dec 6. Epub 2018 Dec 6.

Nanchang Center for Disease Control and Prevention, Nanchang, China.

Background: There is international consensus that benzene exposure is causally related to acute myeloid leukemia (AML), and more recent evidence of association with myelodysplastic syndromes (MDS). However, there are uncertainties about the exposure response, particularly risks by time since exposure and age at exposure.

Methods: In a case-cohort study in 110 631 Chinese workers followed up during 1972-1999 we evaluated combined MDS/AML (n = 44) and chronic myeloid leukemia (n = 18). Read More

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December 2018
2 Reads

Overexpression of IL-11 promotes premalignant gastric epithelial hyperplasia in isolation from germline gp130-JAK-STAT3 driver mutations.

Am J Physiol Gastrointest Liver Physiol 2018 Dec 6. Epub 2018 Dec 6.

Murdoch Childrens Research Institute, Australia.

Expression of the cytokine IL-11 is elevated in human Helicobacter pylori infection and progressively increases with worsening gastric pathology. Additionally, IL-11 is required for tumour development in STAT3 dependent murine models of gastric cancer (GC) and, when administered acutely, causes resolving atrophic gastritis. However, it is unclear whether locally elevated IL-11 ligand expression can, in isolation from oncogenic gp130-JAK-STAT pathway mutations, initiate GC pathogenesis. Read More

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December 2018

Revisiting CLEC12A as leukaemic stem cell marker in AML: highlighting the necessity of precision diagnostics in patients eligible for targeted therapy.

Br J Haematol 2018 Dec 5. Epub 2018 Dec 5.

Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.

Targeted therapy directed against rare disease-propagating leukaemic stem cells (LSCs) is a promising prospect for improving the outcome of acute myeloid leukaemia (AML) patients. Thus, distinguishing LSCs from normal haematopoietic stem and progenitor cells (HSPCs) is essential. The CLEC12A receptor has been proposed as a specific marker of LSCs, and consequently as an appealing treatment target. Read More

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December 2018

Rapid identification of specific DNA aptamers precisely targeting CD33 positive leukemia cells through a paired cell-based approach.

Biomater Sci 2018 Dec 6. Epub 2018 Dec 6.

Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, P.R. China and Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Hangzhou 310058, P.R. China.

Aptamers are short single-stranded DNA or RNA molecules, which have recently been developed for potential broad applications such as clinical therapeutics, diagnosis and tumor-targeted drug delivery. However, the selection of specific aptamers is often unsatisfactory using the classical protein or cell-based SELEX. Herein, we modified the paired cell line approach to identify aptamers targeting leukemia cells expressing the CD33 antigen. Read More

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December 2018

Life-Threatening Hypertriglyceridemia in a Patient on Ruxolitinib and Sirolimus for Chronic Graft-versus-Host Disease.

Case Rep Transplant 2018 4;2018:4539757. Epub 2018 Nov 4.

Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.

Ruxolitinib is an oral selective Janus-associated kinase 1 (JAK1) and JAK2 inhibitor that was initially approved by the FDA in 2014 for treatment of myelofibrosis. In preclinical and retrospective clinical studies, use of ruxolitinib was shown to reduce graft-versus-host-disease (GVHD) in allograft recipients with moderate/severe corticosteroid-dependent or refractory chronic GVHD. While the exact mechanism for action in GVHD is not yet fully understood, prospective studies are ongoing and some patients are receiving ruxolitinib in the setting of steroid refractory GVHD. Read More

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November 2018

Elevated expression of IL-17RB and ST2 on myeloid dendritic cells is associated with a Th2-skewed eosinophilic inflammation in nasal polyps.

Clin Transl Allergy 2018 29;8:50. Epub 2018 Nov 29.

1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.

Background: Interleukin(IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) underlie the crosstalk between epithelial cells and dendritic cells (DCs) during the development of Th2 responses. This study aimed to measure the expressions of IL-17RB, ST2 and TSLPR, receptor of IL-25, IL-33, and TSLP respectively, on myeloid DCs in nasal polyps (NP) and evaluate their association with local Th2 inflammation and disease severity in patients with NP.

Methods: Samples were collected from 30 NP patients and 16 control subjects recruited prospectively. Read More

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November 2018

The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes.

Adv Hematol 2018 1;2018:2458679. Epub 2018 Nov 1.

Medical University of Varna, Varna, Bulgaria.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Read More

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November 2018

Gene expression of , , , and topoisomerase IIα as an indicator of chemotherapy response in AML treated with cytarabine and daunorubicin.

Cancer Manag Res 2018 9;10:5573-5589. Epub 2018 Nov 9.

Department of Pharmacology, Jinnah Medical and Dental College, Karachi, Pakistan.

Purpose: Acute myeloid leukemia patients are commonly treated with cytarabine (Ara-C) and anthracyclines but the sustained remission rate is not very promising. We explored the role of drug-metabolizing enzymes and transporters in the therapeutic response.

Patients And Methods: Bone marrow and peripheral blood samples of 90 newly diagnosed acute myeloid leukemia patients treated with standard 3+7 regimen were analyzed through real-time PCR for expression of human equilibrative nucleoside transporter 1, deoxycytidine kinase, cytidine deaminase (), deoxycytidine monophosphate deaminase () and topoisomerase IIα (). Read More

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November 2018
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Induction of immunosuppressive functions and NF-κB by FLIP in monocytes.

Nat Commun 2018 Dec 5;9(1):5193. Epub 2018 Dec 5.

Department of Medicine, Section of Immunology, University of Verona, Verona, 37134, Italy.

Immunosuppression is a hallmark of tumor progression, and treatments that inhibit or deplete monocytic myeloid-derived suppressive cells could promote anti-tumor immunity. c-FLIP is a central regulator of caspase-8-mediated apoptosis and necroptosis. Here we show that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes. Read More

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December 2018
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Complex mammalian-like haematopoietic system found in a colonial chordate.

Nature 2018 Dec 5. Epub 2018 Dec 5.

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Haematopoiesis is an essential process that evolved in multicellular animals. At the heart of this process are haematopoietic stem cells (HSCs), which are multipotent and self-renewing, and generate the entire repertoire of blood and immune cells throughout an animal's life. Although there have been comprehensive studies on self-renewal, differentiation, physiological regulation and niche occupation in vertebrate HSCs, relatively little is known about the evolutionary origin and niches of these cells. Read More

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December 2018
2 Reads

Depletion of Ars2 inhibits cell proliferation and leukemogenesis in acute myeloid leukemia by modulating the miR-6734-3p/p27 axis.

Leukemia 2018 Dec 5. Epub 2018 Dec 5.

College of Pharmacy, Army Medical University, Chongqing, China.

Ars2 is a component of the nuclear cap-binding complex (CBC) that contributes to microRNA biogenesis and is required for cellular proliferation. Little is known regarding the functional role of Ars2 in cell proliferation and leukemogenesis of acute myeloid leukemia. Here, we show that the elevated expression of Ars2 was observed in acute myeloid leukemia (AML) cell lines and bone marrow samples from AML patients and was correlated with poorer overall survival. Read More

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December 2018
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Human bone marrow assessment by single-cell RNA sequencing, mass cytometry, and flow cytometry.

JCI Insight 2018 Dec 6;3(23). Epub 2018 Dec 6.

Laboratory of Myeloid Malignancies, National Heart Lung and Blood Institute, Bethesda, Maryland, USA.

New techniques for single-cell analysis have led to insights into hematopoiesis and the immune system, but the ability of these techniques to cross-validate and reproducibly identify the biological variation in diverse human samples is currently unproven. We therefore performed a comprehensive assessment of human bone marrow cells using both single-cell RNA sequencing and multiparameter flow cytometry from 20 healthy adult human donors across a broad age range. These data characterize variation between healthy donors as well as age-associated changes in cell population frequencies. Read More

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December 2018
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Direct modulation of the bone marrow mesenchymal stromal cell compartment by azacitidine enhances healthy hematopoiesis.

Blood Adv 2018 Dec;2(23):3447-3461

Department of Medicine III, Technische Universität München, Munich, Germany.

Mesenchymal stromal cells (MSCs) are crucial components of the bone marrow (BM) microenvironment essential for regulating self-renewal, survival, and differentiation of hematopoietic stem/progenitor cells (HSPCs) in the stem cell niche. MSCs are functionally altered in myelodysplastic syndromes (MDS) and exhibit an altered methylome compared with MSCs from healthy controls, thus contributing to disease progression. To determine whether MSCs are amenable to epigenetic therapy and if this affects their function, we examined growth, differentiation, and HSPC-supporting capacity of ex vivo-expanded MSCs from MDS patients in comparison with age-matched healthy controls after direct treatment in vitro with the hypomethylating agent azacitidine (AZA). Read More

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December 2018
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Prognostic role of myeloid-derived suppressor cells in cancers: a systematic review and meta-analysis.

BMC Cancer 2018 Dec 5;18(1):1220. Epub 2018 Dec 5.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Myeloid-derived suppressor cells (MDSCs) is a heterogeneous population of immature myeloid cells, inhibiting both the innate and adaptive immunity. Recent studies validated that MDSCs caused immune suppression and promoted cancer progression through various mechanisms. However, the prognostic value of MDSCs in cancer remains controversial. Read More

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December 2018
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FLAG/FLAG-IDA regimen for children with relapsed/refractory acute leukemia in the era of targeted novel therapies.

J Oncol Pharm Pract 2018 Dec 5:1078155218817816. Epub 2018 Dec 5.

1 Princess Noorah Oncology Center, King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia.

Background: Outcomes of relapsed/refractory childhood acute leukemia remain poor. We analyzed the safety/efficacy of fludarabine, cytarabine, and granulocyte colony stimulating factor, with/without idarubicin (FLAG ± IDA) as salvage therapy compared with recent published results of novel therapies.

Methods: This retrospective study included children aged 1 to 15 years with relapsed/refractory acute leukemia who received FLAG ± IDA salvage therapy from January 2000 to December 2014. Read More

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December 2018

Pharmacological Inhibition of LSD1 for Cancer Treatment.

Molecules 2018 Dec 4;23(12). Epub 2018 Dec 4.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.

Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. Read More

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December 2018

Dimethyl fumarate and vitamin D derivatives cooperatively enhance VDR and Nrf2 signaling in differentiating AML cells in vitro and inhibit leukemia progression in a xenograft mouse model.

J Steroid Biochem Mol Biol 2018 Nov 30. Epub 2018 Nov 30.

Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84105 Beer Sheva, Israel. Electronic address:

Acute myeloid leukemia (AML) is one of the deadliest hematological malignancies without effective treatment for most patients. Vitamin D derivatives (VDDs) - active metabolites 1α,25-dihydroxyvitamin D (1,25D2) and 1α,25-dihydroxyvitamin D (1,25D3) and their analogs - are differentiation-inducing agents which have potential for the therapy of AML. However, calcemic toxicity of VDDs limits their clinical use at doses effective against cancer cells in vivo. Read More

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November 2018
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PARTICIPATION OF VITAMIN D-UPREGULATED PROTEIN 1 (TXNIP)-ASK1-JNK1 SIGNALOSOME IN THE ENHANCEMENT OF AML CELL DEATH BY A POST-CYTOTOXIC DIFFERENTIATION REGIMEN.

J Steroid Biochem Mol Biol 2018 Nov 30. Epub 2018 Nov 30.

Department of Pathology & Laboratory Medicine, Rutgers NJ Medical School, Newark, NJ, United States. Electronic address:

Standard therapy for Acute Myeloid Leukemia (AML) is rarely curative, and several suggested improvements have had little success so far. We have reported that in an in vitro model of a potential therapeutic regimen for AML, the activity of cytarabine (AraC) is enhanced by a sequential treatment with a combination of the vitamin D2 analog Doxercalciferol (D2) and the plant-derived antioxidant carnosic acid (CA) Importantly, the enhancement occurred selectively in patient-derived AML blasts, but not in the normal bone marrow cells. We now demonstrate that TXNIP, previously known as Vitamin D up-regulated protein 1 (VDUP1) [PMID 808674] plays a part in signaling cell death (CD) in this regimen. Read More

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November 2018
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Eomes-expressing T-helper cells as potential target of therapy in chronic neuroinflammation.

Authors:
Shinji Oki

Neurochem Int 2018 Nov 30. Epub 2018 Nov 30.

Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan. Electronic address:

Reserch progresses in understanding the pathogenicity of multiple sclerosis (MS) in the last couple of decade has enabled us to develop new drug entities available in the clinic. However, we still have not succeeded in preventing conversion from relapsing-remitting MS (RR-MS) to secondary progressive MS (SP-MS) and curing this intractable form of MS. Furthermore, diagnosis is usually retrospective and subjective, relying on gradual worsening of neurological signs/symptoms. Read More

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November 2018

Metformin induces CD11b+ cell-mediated growth inhibition of an osteosarcoma: implications for metabolic reprogramming of myeloid cells and antitumor effects.

Int Immunol 2018 Dec 2. Epub 2018 Dec 2.

Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

CD11b+ myeloid subpopulations, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), play crucial roles in the suppression of T-cell-mediated antitumor immunity. Regulation of these cell types is a primary goal for achieving efficient cancer immunotherapy. We found that metformin (Met) induces CD11b+ cell-mediated growth inhibition of a K7M2neo osteosarcoma independent of T cells, as growth inhibition of K7M2neo was still observed in wild type (WT) mice depleted of T cells by antibodies and in SCID; this contrasted with the effect of Met on Meth-A fibrosarcoma, which was entirely T cell-dependent. Read More

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December 2018
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Discovery of donor genotype associated with long-term survival of patients with hematopoietic stem cell transplantation in refractory acute myeloid leukemia.

Leuk Lymphoma 2018 Dec 3:1-7. Epub 2018 Dec 3.

a Department of Internal Medicine , Seoul National University Hospital , Seoul , Korea.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been the only treatment option for acute myeloid leukemia (AML) refractory to induction chemotherapy, with only 10-20% of patients achieving long-term survival. Certain donor genotypes may confer leukemia-clearing effects after allo-HSCT. We performed whole-exome sequencing of five pairs of the germ lines in AML patients who achieved long-term remission after allo-HSCT and in their donors, and found two significant variants: EGFR c. Read More

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December 2018
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Nobiletin down-regulates c-KIT gene expression and exerts anti-leukemic effects on human acute myeloid leukemia cells.

J Agric Food Chem 2018 Dec 3. Epub 2018 Dec 3.

Nobiletin, a dietary citrus flavonoid, has been reported to possess several biological activities, such as anti-oxidant, anti-inflammatory and anti-cancer properties. The aim of this study was to investigate the anti-leukemic effects of nobiletin and its underlying mechanisms on human acute myeloid leukemia (AML) cells. We demonstrated that nobiletin (0-100 μM) significantly reduced cell viability from 100. Read More

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December 2018

The contribution of PTPN22 to rheumatological disease.

Arthritis Rheumatol 2018 Dec 3. Epub 2018 Dec 3.

Department of Medicine, University of California San Diego, 9500 Gilman Drive, MC0656, La Jolla, CA, 92093-0656.

One of the unresolved questions in modern medicine is why certain individuals develop a disorder such as rheumatoid arthritis or lupus, while others do not. Contemporary science holds genetics partly responsible and blames the remainder on environmental and stochastic factors. Among the many genes that increase the risk of autoimmune conditions, the risk allele encoding the W620 variant of PTPN22 is shared between multiple rheumatologic diseases, suggesting a fundamental role in the development of immune dysfunction. Read More

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December 2018

E4F1 silencing inhibits the cell growth through cell-cycle arrest in malignant transformed cells induced by hydroquinone.

J Biochem Mol Toxicol 2018 Dec 1:e22269. Epub 2018 Dec 1.

Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China.

Hydroquinone (HQ), one of the most significant metabolic activation products of benzene in an organism, can cause hematological toxicity, such as acute myeloid leukemia. It is a clear carcinogen that can cause changes in the disorder of cell cycle and cell growth. However, its molecular mechanisms remain unclear. Read More

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December 2018

Combined intracavitary thermotherapy with iron oxide nanoparticles and radiotherapy as local treatment modality in recurrent glioblastoma patients.

J Neurooncol 2018 Dec 1. Epub 2018 Dec 1.

Department of Neurosurgery, University Hospital of Münster, Münster, Germany.

Background: There is an increasing interest in local tumor ablative treatment modalities that induce immunogenic cell death and the generation of antitumor immune responses.

Methods: We report six recurrent glioblastoma patients who were treated with intracavitary thermotherapy after coating the resection cavity wall with superparamagnetic iron oxide nanoparticles ("NanoPaste" technique). Patients underwent six 1-h hyperthermia sessions in an alternating magnetic field and, if possible, received concurrent fractionated radiotherapy at a dose of 39. Read More

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December 2018
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Neutropenic enterocolitis in patients with FLT3 mutated acute myeloid leukemia undergoing induction chemotherapy with midostaurin.

Int J Hematol 2018 Dec 3. Epub 2018 Dec 3.

Department of Hematology and Oncology, Marshall University, 1400 Hal Greer Blvd, Huntington, WV, 25701, USA.

Neutropenic enterocolitis mostly affects patients with acute myeloid leukemia (AML) who get treated with intensive chemotherapy which is associated with prolonged neutropenia; its pathogenesis is not well understood and the main factors in this life-threatening condition appear to be neutropenia, mucosal injury and a weakened immune system as a consequence of intensive chemotherapeutic agents. Midostaurin in combination with chemotherapy became the standard of care for FLT3 mutant AML since its approval by the United States Food and Drug Administration (FDA) in April 2017. Anecdotally in our institution, we noticed the common occurrence of neutropenic colitis in three out of three patients who were treated with midostaurin as part of induction chemotherapy for AML. Read More

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December 2018

The clinical significance of the alternative Wilms tumor gene overexpression-hypermethylation signature in acute myeloid leukemia.

Clin Transl Oncol 2018 Nov 30. Epub 2018 Nov 30.

Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Background: Wilms tumor 1 (WT1) gene is overexpressed in numerous cancers, including acute myeloid leukemia (AML). The alternative WT1 gene (AWT1) is generated from alternative transcription start site in the WT1 first intron and encodes an N-terminal-truncated protein lacking the repressor domain. Although WT1 overexpression is a common feature in AML, the expression levels of the AWT1 and its underlying epigenetic alterations, as well as their clinical relevance in AML remain unknown. Read More

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November 2018
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Myelolytic Treatments Enhance Oncolytic Herpes Virotherapy in Models of Ewing Sarcoma by Modulating the Immune Microenvironment.

Mol Ther Oncolytics 2018 Dec 18;11:62-74. Epub 2018 Oct 18.

Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, OH 43205, USA.

Ewing sarcoma is a highly aggressive cancer that promotes the infiltration and activation of pro-tumor M2-like macrophages. Oncolytic virotherapy that selectively infects and destroys cancer cells is a promising option for treating Ewing sarcoma. The effect of tumor macrophages on oncolytic virus therapy, however, is variable among solid tumors and is unknown in Ewing sarcoma. Read More

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December 2018

Feasibility of treatment discontinuation in chronic myeloid leukemia in clinical practice: results from a nationwide series of 236 patients.

Blood Cancer J 2018 Dec 2;8(10):91. Epub 2018 Dec 2.

Hematology Department, Hospital Universitario La Princesa, Madrid, Spain.

Over half of chronic myeloid leukemia (CML) patients in deep molecular response do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in clinical trials, but its applicability in the real-life setting remains unsettled. We describe the outcomes after TKI discontinuation in a nationwide series of 236 CML patients. Read More

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December 2018
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Clinical impact of clonal hematopoiesis in acute myeloid leukemia patients receiving allogeneic transplantation.

Bone Marrow Transplant 2018 Nov 30. Epub 2018 Nov 30.

Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany.

Age-related somatic mutations linked to clonal hematopoiesis have been found in apparently healthy individuals and increase the risk of developing hematologic malignancies. In acute myeloid leukemia (AML) the clinical relevance of clonal hematopoiesis remains controversial and data on patients with detectable clonal hematopoiesis, consolidated with hematopoietic stem cell transplantation are limited. We analyzed samples from 113 AML patients in complete remission prior to hematopoietic stem cell transplantation for the presence of clonal hematopoiesis-associated mutations. Read More

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November 2018
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LY341495, an mGluR2/3 Antagonist, Regulates the Immunosuppressive Function of Myeloid-Derived Suppressor Cells and Inhibits Melanoma Tumor Growth.

Biol Pharm Bull 2018 ;41(12):1866-1869

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University.

Myeloid-derived suppressor cells (MDSCs) are immunosuppressive myeloid cells found in patients with cancer and in mouse tumor models. They suppress anti-tumor immunity, resulting in the promotion of tumor growth. The relationship between nutrition and cancer has recently been reported by several research groups. Read More

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January 2018
2 Reads

[MET/ERK and MET/JNK Pathway Activation Is Involved in BCR-ABL Inhibitor-resistance in Chronic Myeloid Leukemia].

Authors:
Masanobu Tsubaki

Yakugaku Zasshi 2018 ;138(12):1461-1466

Division of Pharmacotherapy, Faculty of Pharmacy, Kindai University.

Resistance to the breakpoint cluster region-abelson (BCR-ABL) tyrosine kinase inhibitor (TKI), imatinib, poses a major problem in the treatment of chronic myeloid leukemia (CML). Imatinib resistance often results from a secondary mutation in BCR-ABL1. However, the basis of this BCR-ABL1-independent resistance in the absence of such mutation remains to be elucidated. Read More

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January 2018

Depression induced neuropeptide Y secretion promotes prostate cancer growth by recruiting myeloid cells.

Clin Cancer Res 2018 Nov 30. Epub 2018 Nov 30.

Center for New Drug Safety Evaluation and Research, China Pharmaceutical University

Purpose: Psychological depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychological depression alters the immune profiles in prostate cancer.

Experimental Design: We used a murine model of depression in Myc-CaP tumor bearing immune competent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Read More

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November 2018

Treatments targeting MDS genetics: a fool's errand?

Authors:
Amy E DeZern

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):277-285

Division of Hematologic Malignancies, John Hopkins Medicine, Baltimore, MD.

The myelodysplastic syndromes are collectively the most common myeloid neoplasms. Clonal hematopoiesis present in these diseases results in bone marrow failure characteristically seen in patients. The heterogeneity of myelodysplastic syndrome pathobiology has historically posed a challenge to the development of newer therapies. Read More

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November 2018

The MDS genomics-prognosis symbiosis.

Authors:
Aziz Nazha

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):270-276

Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.

Myelodysplastic syndromes (MDS) are clonal disorders characterized by the accumulation of complex genomic abnormalities that define disease phenotype, prognosis, and the risk of transformation to acute myeloid leukemia. The clinical manifestations and overall outcomes of MDS are very heterogeneous with an overall survival that can be measured in years for some patients to a few months for others. Prognostic scoring systems are important staging tools that aid physicians in their treatment recommendations and decision-making and can help patients understand their disease trajectory and expectations. Read More

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November 2018

We do still transplant CML, don't we?

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):177-184

Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom.

The remarkable clinical activity of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has transformed patient outcome. Consequently, allogeneic stem cell transplantation (allo-SCT) is no longer the only treatment modality with the ability to deliver long-term survival. In contrast to the central position it held in the treatment algorithm 20 years ago, allografting is now largely reserved for patients with either chronic-phase disease resistant to TKI therapy or advanced-phase disease. Read More

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November 2018

Molecular monitoring in CML: how deep? How often? How should it influence therapy?

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):168-176

Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.

With the advent of tyrosine kinase inhibitors (TKIs), the goals of therapy in chronic myeloid leukemia (CML) are steadily shifting. Long-term disease control on TKI therapy has been the goal and expectation for most patients. More recently, treatment-free remission (TFR) has entered mainstream practice and is increasingly being adopted as the main goal of therapy. Read More

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November 2018
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The argument for using imatinib in CML.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):161-167

Department of Clinical Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom; and.

June 2018 was the 20th anniversary of the clinical use of the first tyrosine kinase inhibitor (TKI), imatinib, for chronic myeloid leukemia. Since then, the change in prognosis for patients with this disease is one of the major success stories of modern cancer medicine. The dilemmas that face physicians and patients are no longer only those concerned with delaying inevitable progression to the terminal blastic phase or selecting the individuals most likely to benefit from allogeneic stem-cell transplantation; rather, they are now focused also on the choice of TKI, the management of comorbidities and adverse effects, strategies to improve quality of life, and the appropriateness of a trial of therapy discontinuation. Read More

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November 2018
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Managing myelofibrosis (MF) that "blasts" through: advancements in the treatment of relapsed/refractory and blast-phase MF.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):118-126

Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX.

Myelofibrosis (MF) is the most aggressive form of Philadelphia chromosome-negative myeloproliferative neoplasm, and it is complicated by severe symptom burden, thrombotic events, infections, cytopenias, and transformation to acute myeloid leukemia (AML). Ruxolitinib, the first-line therapy for symptomatic or intermediate- and high-prognostic risk MF, has improved overall survival for this population. However, approximately one-half of MF patients will discontinue ruxolitinib by the first few years of therapy due to a spectrum of resistance, intolerance, relapse, or progression to blast phase disease. Read More

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November 2018

Cytotoxic therapy in acute myeloid leukemia: not quite dead yet.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):51-62

Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI.

Given the recent approvals of new agents for acute myeloid leukemia (AML), a clinical trial pipeline stocked with novel therapies, and the rapid integration of imaginative approaches in diseases like acute lymphocytic leukemia and chronic lymphocytic leukemia, it is reasonable to ask whether treatment of AML might finally depart from the classical cytotoxic induction therapy that has been employed since the 1970s. However, for better or worse, in 2018, cytotoxic induction regimens remain the standard of care for most patients. Indeed, the future likely lies in combinations of therapies that act with a spectrum of mechanisms. Read More

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November 2018
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New drugs for acute myeloid leukemia inspired by genomics and when to use them.

Authors:
Daniel A Pollyea

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):45-50

Division of Hematology, University of Colorado School of Medicine, Aurora, CO.

We are several years into the "postdiscovery" era in acute myeloid leukemia (AML) thanks to extensive work involving the sequencing of genomes and exomes of countless patients, which has led to routine comprehensive targeted sequencing in clinical care. The ability to unlock the molecular underpinnings of each patient's disease was supposed to usher in a new treatment era in which each patient was assigned, based on her mutational profile, a personalized cocktail of targeted therapies that would snuff the disease into submission with minimal toxicity. Whether we have fully realized the promise of personalized therapy in AML is unclear. Read More

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November 2018

When to obtain genomic data in acute myeloid leukemia (AML) and which mutations matter.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):35-44

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and.

Mutational profiling has fundamentally changed our approach to patients with acute myeloid leukemia (AML). Patients with AML are routinely profiled for the presence of mutations in , , , and, more recently, In this chapter, we review the role of mutational profiling to help define disease biology in AML, particularly among patients with putatively intermediate-risk disease. We describe the body of evidence supporting the utility of mutational profiling when performed at the time of diagnosis (to identify prognostic and targetable mutations), at the time of complete remission (to assess minimal residual disease as a marker for relapse), and at the time of relapse (to identify therapeutic targets and eligibility for clinical trials). Read More

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November 2018
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