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Ann Diagn Pathol 2021 Jun 5;53:151767. Epub 2021 Jun 5.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.

The t(9;22)(q34;q11.2), also known as the Philadelphia (Ph) chromosome, results in BCR-ABL1 fusion residing on the derivative chromosome 22. This translocation is characteristic of chronic myeloid leukemia, but also can occur in a substantial subset of B acute lymphoblastic leukemia (B-ALL) cases. Read More

Eur J Med Genet 2021 Jun 9:104260. Epub 2021 Jun 9.

Department of Pediatrics III, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; Department of Otorhinolaryngology & Head/Neck Surgery, University Hospital Düsseldorf, Heinrich Heine University, 40225 Düsseldorf, Germany. Electronic address:

Fanconi anemia (FA) due to biallelic mutations in the BRCA2 gene is very rare and associated with an extremely high risk of early-onset of aggressive childhood malignancies, predominantly brain tumors, leukemia, and nephroblastoma. Here, we present a consanguineous family with three affected children of the D1 subtype of FA and describe the clinical consequences of the earliest known biallelic nonsense/stop-gain germ-line mutation in BRCA2, exon 5 c.469A>T, that leads to a premature stop of translation, p. Read More

Ann Hematol 2021 Jun 12. Epub 2021 Jun 12.

Department of Gerodontology and Oral Pathology, Poznan University of Medical Sciences, Bukowska 70, 60-812, Poznań, Poland.

This study was designed to investigate the frequency and severity of oral mucositis in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, in relation to the type of conditioning used. Eighty patients diagnosed with acute myeloid leukemia were assigned to two groups based on the conditioning regimen used before transplantation. The intensity of oral inflammatory lesions induced by chemotherapy (oral mucositis) was evaluated according to a 5-point scale recommended by World Health Organization. Read More

Nat Struct Mol Biol 2021 Jun 10;28(6):487-500. Epub 2021 Jun 10.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Read More

Cancer Gene Ther 2021 Jun 11. Epub 2021 Jun 11.

Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.

Cabozantinib is a potent tyrosine kinase inhibitor with multiple targets including MET, VEGFR2, RET, KIT, and FLT3. Cabozantinib is widely used for the treatment of medullary thyroid cancer and renal cell carcinoma. We recently suggested cabozantinib as a potential therapeutic alternative for acute myeloid leukemia (AML) patients with FLT3-internal tandem duplication (FLT3-ITD). Read More

J Immunol 2021 Jun 11. Epub 2021 Jun 11.

Department of Structural Biology, Stanford University, Stanford, CA;

In the treatment of acute myelogenous leukemia with allogeneic hematopoietic cell transplantation, we previously demonstrated that there is a greater protection from relapse of leukemia when the hematopoietic cell transplantation donor has either the / genotype or a genotype having two or more gene segments. In those earlier analyses, genotyping could only be assessed at the low resolution of gene presence or absence. To give the analysis greater depth, we developed high-resolution sequence-based typing that defines all the alleles and distinguishes the expressed alleles from those that are not expressed. Read More

Cold Spring Harb Mol Case Stud 2021 Jun 11;7(3). Epub 2021 Jun 11.

Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

A 52-yr-old woman presented with therapy-related acute myeloid leukemia. A bone marrow biopsy showed 21% blasts with a myeloid phenotype and no other notable features such as abnormal eosinophils. Routine nanofluidics-based reverse transcriptase polymerase chain reaction (PCR) leukemia translocation panel designed to screen for recurrent genetic abnormalities in acute leukemia detected an inversion 16 transcript variant E. Read More

Leuk Res 2021 Jun 6;109:106638. Epub 2021 Jun 6.

Department of Hematology, Zhengzhou University People's Hospital and Henan Provincial People's Hospital, Henan, People's Republic of China. Electronic address:

Cytoplasmic vacuoles, which are a morphological feature of dysplasia, can be observed under a microscope at initial diagnosis. Recently, this typical morphological feature has been found to be associated with impaired survival. To investigate the clinical significance of the grading of blasts with vacuoles in acute myeloid leukemia (AML), we retrospectively studied 152 patients newly diagnosed with non-M3 AML. Read More

Blood 2021 Jun 11. Epub 2021 Jun 11.

Prinses Máxima Centrum, Utrecht, Netherlands.

Treatment outcomes for pediatric patients with acute myeloid leukemia (AML) have continued to lag behind outcomes reported for children with acute lymphoblastic leukemia (ALL), in part because of the heterogeneity of the disease, a paucity of targeted therapies, and the relatively slow development of immunotherapy compared to ALL. In addition, we have reached the limits of treatment intensity and, even with outstanding supportive care, it is highly unlikely that further intensification of conventional chemotherapy alone will impact relapse rates. However, comprehensive genomic analyses and a more thorough characterization of the leukemic stem cell have provided insights that should lead to tailored and more effective therapies in the near future. Read More

Arch Gynecol Obstet 2021 Jun 11. Epub 2021 Jun 11.

Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 17 Qihelou St, Dongcheng District, Beijing, 100006, China.

Objective: Data on the outcomes of fetus who are exposed to neoadjuvant platinum and paclitaxel chemotherapy during pregnancy are lacking.

Methods: Relevant data were abstracted from patients in our institution, PubMed, Embase and Cochrane Library databases. The primary assessment was the frequency of fetal death and congenital abnormalities. Read More

Blood 2021 Jun 3. Epub 2021 Jun 3.

Vanderbilt University School of Medicine, Nashville, Tennessee, United States.

Recently, encouraging data provided long-awaited hope for gene therapy as a cure for sickle cell disease (SCD). Nevertheless, the suspension of the bluebird bio gene therapy trial (ClinicalTrials.gov: NCT02140554) after participants developed acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) is concerning. Read More

Blood 2021 Jun 3. Epub 2021 Jun 3.

Karlsruhe Institute for Technology, Eggenstein-Leopoldshafen, Germany.

Acute myeloid leukemia (AML) has a poor prognosis under the current standard of care. In recent years, venetoclax, a BCL-2 inhibitor, was approved to treat patients, ineligible for intensive induction chemotherapy. Complete remission rates with venetoclax-based therapies are, however, hampered by minimal residual disease (MRD) in a proportion of patients, leading to relapse. Read More

Blood 2021 Jun 3. Epub 2021 Jun 3.

The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.

While clonal hematopoiesis (CH) can precede the development of acute myeloid leukemia (AML), it can also persist after achieving remission. Long-term clonal dynamics and clinical implications of persistent CH are not well understood. Here, we studied the prevalence, dynamics and clinical implications of post-remission CH in 164 AML patients who attained complete remission after induction chemotherapies. Read More

Medicine (Baltimore) 2021 Jun;100(23):e26098

Affiliated Hospital of Shandong University of Traditional Chinese Medicine.

Background: Acute myeloid leukemia (AML) is the most common malignant tumor of the hematopoietic system, which seriously threatens the lives of patients. Most AML patients have acute onset, severe condition, and poor prognosis. The present study aimed to comprehensively evaluate the effectiveness and safety of chemotherapy combined with different doses of interleukin-2 (IL-2) maintenance treatments in AML by Bayesian network meta-analysis (NMA). Read More

Cell Death Discov 2021 Jun 10;7(1):137. Epub 2021 Jun 10.

Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Over the last 50 years, there has been a steady improvement in the treatment outcome of acute myeloid leukemia (AML). However, median survival in the elderly is still poor due to intolerance to intensive chemotherapy and higher numbers of patients with adverse cytogenetics. Fadraciclib (CYC065), a novel cyclin-dependent kinase (CDK) 2/9 inhibitor, has preclinical efficacy in AML. Read More

Biomed Pharmacother 2021 Jun 8:111652. Epub 2021 Jun 8.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Center South University, Changsha 410008, Hunan, PR China. Electronic address:

Chemotherapy resistance remains to be the primary barrier to acute myeloid leukemia (AML) treatment failure. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been well established as a truly pleiotropic transcription factor. Inhibition of Nrf2 function increases the sensitivity of various chemotherapeutics and overcomes chemoresistance effectively. Read More

Biomark Res 2021 Jun 10;9(1):46. Epub 2021 Jun 10.

Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, Jinan University, 510632, Guangzhou, PR China.

Myelodysplastic syndrome (MDS) is an aggressive and genetically heterogeneous disease with poor prognosis. Cellular immune disorder is a common characteristic of this disease and is thought to be related to clinical outcome. Alterations in T cell clonal expansion and T cell dysfunction has been detected in MDS patients. Read More

Stem Cell Res 2021 May 25;54:102404. Epub 2021 May 25.

Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China. Electronic address:

Objective: ediatric acute leukemia (AL) is the most common hematological malignancy in childhood. However, the limitation of clinical specimens hindered the progress of research. Therefore, new research platforms are urgently needed to establish and clarify the pathogenesis of pediatric AL, and it is necessary to try to find novel targeted therapies for the clinical use. Read More

Blood 2021 Jun 10. Epub 2021 Jun 10.

Perelman School of Medicine at the University of Pennsylvania, United States.

Internal tandem duplication within FLT3 (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and correlates with poor prognosis. While FLT3 receptor tyrosine kinase is activated at the plasma membrane to transduce PI3K/AKT and RAS/MAPK signaling, FLT3-ITD resides in the endoplasmic reticulum (ER) and triggers constitutive STAT5 phosphorylation. Mechanisms underlying this aberrant FLT3-ITD subcellular localization or its impact on leukemogenesis remain poorly established. Read More

Blood 2021 Jun 10. Epub 2021 Jun 10.

University Hospital Ulm, Ulm, Germany.

Patients with acute myeloid leukemia (AML) have conventionally received more "intense" therapy than patients with myelodysplastic syndromes (MDS). Although less intense therapies are being used more often in AML, the AML-MDS dichotomy remains, with the presence of ≥ 20% myeloblasts in marrow or peripheral blood generally regarded as defining AML. Consequently, patients with 19% blasts are typically ineligible for AML studies, with patients with 21% blasts ineligible for MDS studies. Read More

Blood 2021 Jun 10. Epub 2021 Jun 10.

University of Edinburgh, Edinburgh, United Kingdom.

t(4;11) MLL-AF4 acute leukemia is one of the most aggressive malignancies in the infant and pediatric population, yet we have little information on the molecular mechanisms responsible for disease progression. This impairs the development of therapeutic regimens that can address the aggressive phenotype and lineage plasticity of MLL-AF4-driven leukemogenesis. This study highlights novel mechanisms of disease development by focusing on two microRNAs upregulated in leukemic blasts from primary patient samples: miR-130b and miR-128a. Read More

Ann Hematol 2021 Jun 10. Epub 2021 Jun 10.

Department of Nutrition and Natural Products, Migal-Galilee Technology Center, PO Box 831, 11016, Kiryat Shmona, Israel.

Resistance remains the major clinical challenge for the therapy of Philadelphia chromosome-positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common "gatekeeper" mutation T315I. Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia. Read More

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan, R.O.C.

Cytarabine is a key chemotherapy drug for treating leukemia; however, chemotherapy‑induced multidrug resistance is a major cause of therapy failure or tumor recurrence. Current medical treatment strategies still cannot address the issue of multidrug resistance phenotypes in the treatment of leukemia. Curcumin counteracts tumor development by inducing apoptosis in cytarabine‑resistant acute myeloid leukemia cells. Read More

Nat Cancer 2020 Apr 20;1(4):410-422. Epub 2020 Apr 20.

Department of Pharmacology, University of California San Diego, School of Medicine, La Jolla, CA, USA.

Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in this disease. Among these, RNA-binding proteins (RBPs) in general, and the double-stranded RBP Staufen2 (Stau2) in particular, emerged as critical regulators of myeloid leukemia. Read More

Front Oncol 2021 24;11:678824. Epub 2021 May 24.

Cellular Signalling Laboratory, Department of Biomedical Sciences (DIBINEM), University of Bologna, Bologna, Italy.

Polyphosphoinositides (PPIns) and their modulating enzymes are involved in regulating many important cellular functions including proliferation, differentiation or gene expression, and their deregulation is involved in human diseases such as metabolic syndromes, neurodegenerative disorders and cancer, including Acute Myeloid Leukemia (AML). Given that PPIns regulating enzymes are highly druggable targets, several studies have recently highlighted the potential of targeting them in AML. For instance many inhibitors targeting the PI3K pathway are in various stages of clinical development and more recently other novel enzymes such as PIP4K2A have been implicated as AML targets. Read More

Sci Rep 2021 Jun 9;11(1):12209. Epub 2021 Jun 9.

Department of Hematology, Tottori Prefectural Central Hospital, 730 ezu, Tottori City, Tottori, 680-0901, Japan.

Patients with hematological disorders are treated with multiple cycles of chemotherapy. As a result, they often require multiple insertions of the peripherally inserted central catheter (PICC) for prolonged periods of time. Although PICCs have been widely used worldwide in various patients, the safety and feasibility of the multiple insertions of the PICC in this population have not been fully verified. Read More

Sci Rep 2021 Jun 9;11(1):12148. Epub 2021 Jun 9.

Translational Innovation Platform Oncology and Immuno-Oncology, EMD Serono Research & Development Institute, Inc, Billerica, MA, USA.

Peposertib (M3814) is a potent and selective DNA-PK inhibitor in early clinical development. It effectively blocks non-homologous end-joining repair of DNA double-strand breaks (DSB) and strongly potentiates the antitumor effect of ionizing radiation (IR) and topoisomerase II inhibitors. By suppressing DNA-PK catalytic activity in the presence of DNA DSB, M3814 potentiates ATM/p53 signaling leading to enhanced p53-dependent antitumor activity in tumor cells. Read More

Rinsho Ketsueki 2021 ;62(5):352-359

Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University.

STAG2 and other cohesin complex components are mutated in ∼10-15% of myeloid neoplasms, particularly in myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia. STAG2 mutations often coincide with other driver mutations, such as RUNX1, SRSF2, and ASXL1, suggesting a strong functional interaction among these mutations in myeloid neoplasms. To elucidate the mechanism of cohesin-induced leukemogenesis, we generated Stag2 conditional knockout (KO) mice but they only exhibited relatively mild hematopoietic abnormalities and did not develop lethal myeloid neoplasms. Read More

Occup Environ Med 2021 Jun 9. Epub 2021 Jun 9.

Epidemiology, The University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, USA.

Objective: To evaluate exposure-response between 1,3-butadiene, styrene and lymphohaematopoietic cancers in an updated cohort of workers at six North American plants that made synthetic rubber polymers.

Methods: Employees were followed from 1943 through 2009 to determine mortality outcomes. Cox regression analyses estimated rate ratios (RRs) and 95% CIs by quartile of cumulative exposure to butadiene or styrene, measured in parts per million-years (ppm-years), and exposure-response trends for all leukaemia, lymphoid leukaemia, myeloid leukaemia, acute myeloid leukaemia, non-Hodgkin's lymphoma (NHL), multiple myeloma and all B-cell malignancies. Read More

Clin Lymphoma Myeloma Leuk 2021 May 11. Epub 2021 May 11.

Clinical Pathology and Oncologic Laboratory Medicine Department, National Cancer Institute, Cairo University, Egypt.

Background: FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is a molecular genetic alteration significantly affecting the clinical outcome in patients with acute myeloid leukemia (AML). FLT3-ITD mutations are characterized by variable mutant-to-wild allelic ratios (ARs) and sizes of the duplicated sequences. The size of the inserted sequence may vary from a few to hundreds of nucleotides. Read More