Search Our Scientific Publications & Authors

Leuk Res Rep 2020 8;14:100211. Epub 2020 Jun 8.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Curr Health Sci J 2020 Jan-Mar;46(1):23-30. Epub 2020 Mar 31.

University of Medicine and Pharmacy of Craiova, Romania.

Oxidative stress (OS) implies an imbalance between the amount of tissue level of prooxidant and antioxidant compounds. It is involved in the pathophysiology of multiple pathological entities (neoplasms, disorders of carbohydrate and lipid metabolism, cardiovascular and renal pathology etc.), as well as in the pharmacokinetics of specific treatments for these pathologies. Read More

Hematol Transfus Cell Ther 2020 Jul 1. Epub 2020 Jul 1.

Pontifícia Universidade Católica de Campinas, Faculdade de Medicina, SP, Brazil.

This manuscript summarizes the results of the consensus meeting composed of hematologists and cardiologists to establish recommendations for the prevention and follow-up of cardiovascular (CV) risk in patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKIs) from the point of view of clinical practice and from the perspective of hematology consultation. In the first medical appointment, the CV risk factors should be identified to perform the baseline risk stratification, based on the Brazilian Guideline of Dyslipidemia and Atherosclerosis Prevention Update (risk levels: very high, high, intermediate and low). Once stratified, the treatment of the CV risk factors should be administered. Read More

J Chem Inf Model 2020 Jul 5. Epub 2020 Jul 5.

Department of Chemistry, Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina 27695, United States.

Imatinib, a 2-phenylaminopyridine-based BCR-ABL tyrosine kinase inhibitor, is a highly effective drug for treating Chronic Myeloid Leukemia (CML). However, cases of drug resistance are constantly emerging due to various mutations in the ABL kinase domain; thus, it is crucial to identify novel bioactive analogues. Reliable QSAR models and molecular docking protocols have been shown to facilitate the discovery of new compounds from chemical libraries prior to experimental testing. Read More

Pharmacol Res 2020 Jun 30:105058. Epub 2020 Jun 30.

Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea. Electronic address:

Despite the discovery of tyrosine kinase inhibitors (TKIs) for the treatment of breakpoint cluster region-Abelson (BCR-ABL) cancer types, patients with chronic myeloid leukemia (CML) treated with TKIs develop resistance and severe adverse effects. Combination treatment, especially with a histone deacetylase (HDAC) 6 inhibitor (HDAC6i), appears to be an attractive option to prevent TKI resistance, considering the potential capacity of an HDAC6i to diminish BCR-ABL expression. We first validated the in vivo anti-cancer potential of the compound 7b by significantly reducing the tumor burden of BALB/c mice xenografted with K-562 cells, without notable organ toxicity. Read More

Exp Oncol 2020 06;42(2):109-114

Institute of Molecular Biology and Genetics NAS of Ukraine, Kyiv 03143, Ukraine.

Aim: To analyze interaction of ubiquitin specific peptidase 1 (USP1) with Bcr-Abl and to assess the relation between USP1 functional activity and Bcr-Abl expression in K562 chronic myeloid leukemia cells.

Materials And Methods: The interaction between USP1 and Bcr-Abl in K562 cells was analyzed by co-immunoprecipitation, Western blot analysis, and confocal microscopy.

Results: A direct interaction between Bcr-Abl oncoprotein and USP1 protein in K562 cells was established by co-immunoprecipitation. Read More

Pediatr Dermatol 2020 Jun 29. Epub 2020 Jun 29.

Department of Dermatology, University Hospital La Paz, Madrid, Spain.

Nilotinib is a new multitargeted tyrosine kinase inhibitor, which is used to treat chronic myelogenous leukemia when intolerance or recurrence to imatinib occurs. We report the case of a 14-year-old patient being treated with nilotinib who developed a keratosis pilaris-like eruption. This cutaneous adverse effect is a rare but increasingly reported side effect of this therapy. Read More

Cureus 2020 Jun 23;12(6):e8788. Epub 2020 Jun 23.

Hematology and Oncology, Creighton University Arizona Health Education Alliance/Valleywise Health Medical Center, Phoenix, USA.

Chronic myeloid leukemia (CML) represents a common condition in the spectrum of myeloproliferative disorders (MPD). It classically exhibits leukocytosis, but rarely presents with isolated thrombocytosis. This paper is designed to review the clinicopathologic features, treatment, and outcomes of patients with CML who present with isolated thrombocytosis. Read More

Cancer Treat Rev 2020 May 16;88:102026. Epub 2020 May 16.

Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Progress in cancer therapy changed the outcome of many patients and moved therapy from chemotherapy agents to targeted drugs. Targeted drugs already changed the clinical practice in treatment of leukemias, such as imatinib (BCR/ABL inhibitor) in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), ibrutinib (Bruton's tyrosine kinase inhibitor) in chronic lymphocytic leukemia (CLL), venetoclax (BCL2 inhibitor) in CLL and acute myeloid leukemia (AML) or midostaurin (FLT3 inhibitor) in AML. In this review, we focused on DNA damage response (DDR) inhibition, specifically on inhibition of ATR-CHK1 pathway. Read More

Asian Pac J Cancer Prev 2020 Jun 1;21(6):1545-1550. Epub 2020 Jun 1.

Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/ Dr Sardjito General Hospital, Yogyakarta, Indonesia.

The aim of this study was analyzing the BCR-ABL transcript types of patients with chronic myeloid leukemia (CML) in Dr Sardjito General Hospital, Yogyakarta, Indonesia. This study is very relevant because the data concerning BCR-ABL gene transcript types is very limited in Indonesia. Furthermore, it is important for patient's management, particularly in defining the tyrosine kinase inhibitors (TKIs) therapy and monitoring after therapy. Read More

Int J Mol Sci 2020 Jun 23;21(12). Epub 2020 Jun 23.

Dipartimento di Farmacia Scienze del Farmaco Università degli Studi di Bari "Aldo Moro", via Orabona 4, Bari 70125, Italy.

The therapeutic approach to Chronic Myeloid Leukemia (CML) has changed since the advent of the tyrosine kinase inhibitor (TKI) imatinib, which was then followed by the second generation TKIs dasatinib, nilotinib, and, finally, by ponatinib, a third-generation drug. At present, these therapeutic options represent the first-line treatment for adults. Based on clinical experience, imatinb, dasatinib, and nilotinib have been approved for children even though the studies that were concerned with efficacy and safety toward pediatric patients are still awaiting more specific and high-quality data. Read More

Br J Haematol 2020 Jun 24. Epub 2020 Jun 24.

Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

J Cardiovasc Echogr 2020 Apr 10;30(Suppl 1):S17-S25. Epub 2020 Apr 10.

Cardiology Department, Hospital 'Bianchi Melacrino Morelli' Reggio Calabria, Italy.

Peripheral artery disease (PAD) and stroke can occur as vascular complication of anticancer treatment. Although the mechanisms, monitoring, and management of cardiotoxicities have received broad attention, vascular toxicities remain often underrecognized. In addition, the development of new chemotherapeutic drugs bears the risk of vasotoxicities that are yet to be identified and may not be realized with short-term follow-up periods. Read More

Biomed Pharmacother 2020 Jun 17;129:110390. Epub 2020 Jun 17.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Chidamide is a novel selective histone deacetylase inhibitor (HDACi) with promising activity in hematological malignancies, but its role in chronic myeloid leukemia (CML) was marginally addressed. In this study, we firstly demonstrated that chidamide alone inhibited CML cells proliferation, induced apoptosis and cell cycle arrest. Further, chidamide combined with imatinib (IM) induced synergistic lethality in CML cell line KBM5, as well as IM-resistant CML cells KBM5, associated with a marked reduction of Bcr-Abl kinase activity and acetyl-histone H3 expression. Read More

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Jun;28(3):842-848

Department of Clinical Laboratorial Examination, The Second Affiliated Hospital of Xi'an Medical University, Xi'an 710038, Shaanxi Province, China,E-mail:

Objective: To analyze the diagnostic value of multiple reverse transcription-polymerase chain reaction (RT-PCR) for detecting different fusion genes in children with primary acute lymphoblastic leukemia (ALL).

Methods: The clinical data of 80 children with ALL treated in the 2 affiliated hospital of Xi'an Medical College from September 2012 to September 2017 were collected and retrospectively analyzed. Immunophenotype, chromosome karyotype and fusion gene were analyzed. Read More

J Hematol Oncol 2020 Jun 18;13(1):80. Epub 2020 Jun 18.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: The Philadelphia chromosome (Ph), which leads to the creation and expression of the fusion gene product BCR-ABL, underlines the pathogenesis of chronic myelogenous leukemia (CML) and a fraction of adult and pediatric acute B-lymphoblastic leukemia (B-ALL). The BCR-ABL tyrosine kinase inhibitors (TKIs) have shown a remarkable clinical activity in patients with CML, but their efficacy in treating Ph B-ALL is limited. Identifying additional therapeutic targets is important for the effective treatment of Ph B-ALL. Read More

Cureus 2020 Jun 7;12(6):e8498. Epub 2020 Jun 7.

Hematology and Oncology, Creighton University Arizona Health Education Alliance/Valleywise Health, Phoenix, USA.

Chronic myeloid leukemia (CML) is one of the classic types of myeloproliferative neoplasms. It typically manifests with leukocytosis, but rarely with isolated thrombocytosis. Here we describe a unique case of isolated thrombocytosis as an initial presentation of CML in a 21-year-old woman, where the BCR-ABL1 fusion gene was detected in bone marrow (BM) aspiration and biopsy specimen after a negative peripheral blood (PB) fluorescence in situ hybridization testing. Read More

Cancers (Basel) 2020 May 29;12(6). Epub 2020 May 29.

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Chronic myelogenous leukemia (CML) is the most common type of leukemia in adults, and more than 90% of CML patients harbor the abnormal Philadelphia chromosome (Ph) that encodes the BCR-ABL oncoprotein. Although the ABL kinase inhibitor (imatinib) has proven to be very effective in achieving high remission rates and improving prognosis, up to 33% of CML patients still cannot achieve an optimal response. Here, we used CRISPR/Cas9 to specifically target the - junction region in K562 cells, resulting in the inhibition of cancer cell growth and oncogenesis. Read More

Hematol Transfus Cell Ther 2020 May 25. Epub 2020 May 25.

Departamento de Hematologia, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address:

Introduction: Chronic Myeloid Leukemia (CML) is a myeloproliferative disease that affects mainly adults between 50 and 55 years. In Brazil, information from the Sistema Único de Saúde (SUS) Outpatient Information System indicates that 12,531 patients had the Autorização de Procedimento Ambulatorial (APAC) approved for the CML treatment in 2017. Disease monitoring through molecular response evaluation is critical to the care of CML patients. Read More

Cancer Immunol Immunother 2020 May 30. Epub 2020 May 30.

Department of Hematology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Malignant cells can increase in number using immune escape mechanisms such as immune checkpoints. In this study, we evaluated the expression of an immune checkpoint programmed death 1 (PD-1) on T-cell subsets in chronic myeloid leukemia (CML). We obtained bone marrow aspirate samples from CML patients and from individuals without evidence of hematologic malignancies (controls). Read More

Cureus 2020 Apr 25;12(4):e7826. Epub 2020 Apr 25.

Oncology, Jinnah Hospital, Lahore, PAK.

Introduction: The hallmark of chronic myeloid leukemia (CML) is the development of the fusion gene, BCR-ABL which has unopposed tyrosine kinase activity. The first tyrosine kinase inhibitor (TKI) imatinib is claimed to have superior efficacy and side effect profile as compared to traditional treatment options. This study was conducted to see our patients' molecular response to imatinib treatment. Read More

Turk J Pharm Sci 2020 Feb 19;17(1):49-55. Epub 2020 Feb 19.

Kumamoto University, School of Pharmacy, Department of Bioorganic Medicinal Chemistry, Kumamoto, Japan.

Objectives: Chronic myelogenous leukemia (CML) is a type of blood cancer that is initially treated with imatinib (first Abl kinase inhibitor). However, some patients with CML develop imatinib resistance. Several new generation drugs have been developed, but do not overcome this problem. Read More

Infect Dis Clin North Am 2020 Jun;34(2):245-256

Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, HWCRC - 4th Floor, 4100 John R, Detroit, MI 48201, USA.

Tyrosine kinase inhibitors represent the standard of care for several diseases and drug targets in hematologic malignancies. Infectious complications vary by disease status and prior therapy, but overall incidence of infections generally is low. In chronic diseases, such as chronic myeloid leukemia and chronic lymphocytic leukemia, patients can remain on tyrosine kinase inhibitor therapy for many years, with few infectious complications from therapy. Read More

Clin Epigenetics 2020 May 19;12(1):69. Epub 2020 May 19.

Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea.

Background: Chronic myeloid leukemia (CML) pathogenesis is mainly driven by the oncogenic breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) fusion protein. Since BCR-ABL displays abnormal constitutive tyrosine kinase activity, therapies using tyrosine kinase inhibitors (TKis) such as imatinib represent a major breakthrough for the outcome of CML patients. Nevertheless, the development of TKi resistance and the persistence of leukemia stem cells (LSCs) remain barriers to cure the disease, justifying the development of novel therapeutic approaches. Read More

Cancers (Basel) 2020 May 15;12(5). Epub 2020 May 15.

Department of Pharmacy, Namur Research Institute for Life Sciences (NARILIS), Namur Thrombosis and Hemostasis Center (NTHC), University of Namur, 5000 Namur, Belgium.

Large randomized clinical trials and prior meta-analyses indicate that second-generation BCR-ABL tyrosine kinase inhibitors (TKIs) improve surrogate biomarkers in patients with chronic myeloid leukemia (CML) without providing survival benefits. The objective is to evaluate the long-term efficacy and the occurrence of vascular occlusion with second-generation BCR-ABL TKIs compared with imatinib in patients with CML. Three scientific databases, a clinical registry and abstracts from congress were searched to identify all randomized controlled trials that compared a second-generation BCR-ABL TKI to imatinib in patients with CML. Read More

Clin Cancer Res 2020 May 12. Epub 2020 May 12.

The Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois.

Treating BCR-ABL-positive chronic myeloid leukemia remains impeded by the development of clinical resistance to imatinib. It has been demonstrated that berberine, a plant alkaloid, has activity against imatinib-resistant BCR-ABL mutants by inducing autophagic degradation of BCR-ABL, thereby preventing the acquisition of drug-resistant mutations.. Read More

Zhonghua Xue Ye Xue Za Zhi 2019 07;40(7):613

Henan Provincial Key Laboratory of Hematopathology, Institute of Haematology, Henan Provincial People's Hospital, Zhengzhou 450002, China.

Zhonghua Xue Ye Xue Za Zhi 2019 Jul;40(7):547-553

Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China.

To compare the clinical features between the 2 cohorts developing myelodysplastic syndrome or acute myeIogenous Ieukemia in Philadelphia chromosome-negative cells (Ph(-) MDS/AML) and maintaining disease stable in the patients with Philadelphia chromosome-positive chronic myeloid Ieukemia (Ph(+) CML) who had clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph(-)) during tyrosine kinase inhibtor (TKI) - therapy. We retrospectively analyzed Ph(+) CML patients who developed CCA/Ph(-) during TKI-therapy from May 2001 to December 2017. Data of CCA/Ph(-) 63 patients, including 7 progressing to Ph(-) MDS/AML and 56 remaining disease stable were collected. Read More

Microcirculation 2020 May 12. Epub 2020 May 12.

Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United States.

Objective: Treatment with BCR-ABL tyrosine kinase inhibitors (TKIs) is the standard of care for patients with chronic myeloid leukemia, however evidence indicates these compounds may have cardiovascular side-effects. This study sought to determine if ex vivo exposure of human adipose arterioles to the BCR-ABL TKIs imatinib and nilotinib causes endothelial dysfunction.

Methods: Human adipose arterioles were incubated overnight in cell culture media containing vehicle (PBS), imatinib (10 µM) or nilotinib (100 µM). Read More

CEN Case Rep 2020 May 9. Epub 2020 May 9.

Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.

A 52-year-old woman was diagnosed with chronic myeloid leukemia. Treatment with dasatinib, a second-generation Bcr-Abl tyrosine kinase inhibitor, was initiated, and complete cytogenetic remission was achieved. Two years later, proteinuria occurred, and the urinary protein level increased gradually in the next 3 years. Read More

Medicine (Baltimore) 2020 May;99(19):e19962

Department of Internal Medicine.

Introduction: After tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 were introduced for the treatment of chronic myeloid leukemia, clinical outcomes have improved dramatically. However, together with the increase in the survival rate, a more frequent occurrence of secondary malignancies has been observed as well. TKIs have been demonstrated to be a risk factor of malignancies such as non-Hodgkin lymphoma, prostate cancer, and skin cancer. Read More

Anticancer Res 2020 May;40(5):2457-2465

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

The introduction of tyrosine kinase inhibitors (TKIs) directed against the catalytic activity of the ABL tyrosine kinase has considerably improved the outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease. Indeed, these individuals currently show a life-expectancy comparable to those of healthy subjects. Currently, five TKIs (imatinib, dasatinib, nilotinib, bosutinib and ponatinib) are approved for the treatment of CML and can be used as first, second or further lines of treatment according to disease risk scores, patient comorbidities and the presence of known TKI resistance mechanisms. Read More

J Int Med Res 2020 May;48(5):300060520919237

Department of Hematology, Lanzhou University Second Hospital, Lanzhou, Gansu, People's Republic of China.

Blast crisis develops in a minority of patients with chronic myeloid leukemia even in the era of tyrosine kinase inhibitor (TKI) therapy. Reports suggest that we know little about the mechanism of BCR-ABL and AML1-ETO co-expression in blast crisis of chronic myeloid leukemia, and that other chromosomal abnormalities also coexist. Here, we document an unusual and interesting case of a 51-year-old female diagnosed in the chronic phase of chronic myeloid leukemia. Read More

Pediatr Hematol Oncol 2020 May 4:1-6. Epub 2020 May 4.

Pediatric Hematology-Oncology Unit, Dept. of Pediatrics, Advanced Pediatrics Center, Chandigarh, India.

Imatinib-induced tyrosine kinase inhibition extends beyond the BCR-ABL mutation, resulting in adverse effects. We evaluated hypogammaglobulinemia as a potential 'off-target' action of imatinib in children with CML. A cross-sectional, observational study was performed. Read More

J Cancer Res Ther 2020 Jan-Mar;16(1):173-176

Department of Hematology, SGPGI, Lucknow, Uttar Pradesh, India.

Myelodysplastic syndromes (MDSs) are characteristically defined by the presence of specific karyotypic abnormalities, based on which they have been prognosticated. Translocation t(9;22)(q34;q11.2) (Philadelphia positive [Ph +ve]) and corresponding BCR-ABL fusion transcript is the defining parameter of chronic myeloid leukemia. Read More

J Cancer Res Ther 2020 Jan-Mar;16(1):150-156

Department of Hematology, Ege University, School of Medicine, Izmir, Turkey.

Objective: Tyrosine kinase inhibitors (TKIs) which efficiently inhibit BCR-ABL are highly effective for clinical treatment of chronic myeloid leukemia (CML), but development of resistance to TKIs is a big challenge to treatment. Sunitinib is a multitargeted TKI targeting vascular endothelial growth factor receptor and is defined a safe and effective candidate target, but its effect on other signaling pathways is unknown. To investigate the cytotoxic and apoptotic effect of sunitinib in CML cell model K-562 on JAK-STAT signaling pathway components, suppressor genes and oncogenes, hematopoiesis-related genes, cell cycle and VEGF pathway components, and mRNA level expression changes was aimed. Read More

J Bras Nefrol 2020 Apr 27. Epub 2020 Apr 27.

Dr.RMLIMS, Department of Pathology, Vibhuti Khand, Gomti Nagar, Lucknow, 226010, India.

Imatinib, which inhibits tyrosine kinase activity of Bcr-Abl protein, is a standard form of treatment for chronic myeloid leukemia (CML). Through its immunomodulatory effect it affects T cell function in a number of ways. It inhibits antigen-induced T cell activation and proliferation. Read More

Oncology 2020 29;98(7):445-451. Epub 2020 Apr 29.

Department of Surgical, Oncological, and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

Background: Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs.

Methods: A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3. Read More

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Apr;28(2):430-435

Department of Blood Transfusion, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, Fujian Province, China.

Objective: To investigate the relationship between long non-coding RNA (LncRNA) PANTR1 and imatinib resistance in chronic myeloid leukemia cell line K562 and its mechanism.

Methods: K562 control cells (Control) and K562 imatinib resistant cells (ImR) were cultured. Two siRNA vectors targeting PANTR1 and control vectors were transfected into K562-ImR cells by lentivirus as ImR-siPA#1, ImR-siPA#2 and ImR-siControl cells, respectively. Read More

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Apr;28(2):365-370

Department of Hematology, The First Affiliated Hospital of Kunming Medical University,Kunming 650032, Yunnan Province, China,Yunnan Hematological Disease Research Center, Kunming 650032, Yunnan Province, China,E-mail:

Objective: To investigate the biological effects and mechanism of WNK1 on K562 cells through regulating MAPK7.

Methods: Cells were routinely cultured in vitro, the expression of WNK1 and MAPK7 in different blood tumor cell lines was analyzed by RT-qPCR and Western blot analysis.K562 cells were transfected with siRNA-WNK1 lentivirus. Read More

Cancer Sci 2020 Apr 21. Epub 2020 Apr 21.

Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.

To elucidate dynamic changes in native BCR-ABL and alternatively spliced tyrosine kinase inhibitor (TKI)-resistant but function-dead BCR-ABL variant, following commencement or discontinuation of TKI therapy, each transcript was serially quantified in patients with chronic myeloid leukemia (CML) by deep sequencing. Because both transcripts were amplified together using conventional PCR system for measuring International Scale (IS), deep sequencing method was used for quantifying such BCR-ABL variants. At the initial diagnosis, 7 of 9 patients presented a small fraction of cells possessing BCR-ABL , accounting for 0. Read More

Vasc Med 2020 Jun 17;25(3):246-254. Epub 2020 Apr 17.

Department of Medicine, Division of Cardiology, University of Alabama at Birmingham, Birmingham, AL, USA.

Tyrosine kinase inhibitors (TKIs) of the BCR-ABL fusion protein have dramatically changed the mortality of chronic myeloid leukemia (CML) but they carry a risk of serious vascular morbidity. While TKIs do not cure CML, daily oral administration of a TKI can control CML and TKIs are chronic medications. Interestingly, vascular complications can occur at any time a patient is on a TKI. Read More

Acta Haematol 2020 Apr 14:1-7. Epub 2020 Apr 14.

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

Background: Philadelphia chromosome-positive (Ph+) advanced leukemias, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) in myeloid blast phase (MBP), have poor outcomes. Venetoclax has shown synergism with BCR-ABL1 tyrosine kinase inhibitors (TKI) in preclinical studies. However, clinical activity of venetoclax and TKI-based regimens is unknown. Read More

Cancer Cell 2020 Apr;37(4):530-542

Division of Hematology/Medical Oncology, Knight Cancer Insitute, Oregon Health & Science University, Portland, OR, USA.

Chronic myeloid leukemia (CML), caused by constitutively active BCR-ABL1 fusion tyrosine kinase, has served as a paradigm for successful application of molecularly targeted cancer therapy. The development of the tyrosine kinase inhibitor (TKI) imatinib allows patients with CML to experience near-normal life expectancy. Specific point mutations that decrease drug binding affinity can produce TKI resistance, and second- and third-generation TKIs largely mitigate this problem. Read More

Cancer Lett 2020 Jul 10;482:44-55. Epub 2020 Apr 10.

Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated By Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China. Electronic address:

Although targeted therapy using tyrosine kinase inhibitors (TKIs) has made remarkable progress in treating chronic myeloid leukemia (CML), this disease remains largely incurable, warranting further investigation of new therapeutic strategies. BCR-ABL is a highly specific tumor antigen in CML and provides an attractive opportunity for vaccination therapy. Exogenous antigens must be presented on MHC class I molecules-via a process termed cross-presentation-to activate specific cytotoxic T lymphocyte response. Read More

Cureus 2020 Mar 9;12(3):e7217. Epub 2020 Mar 9.

Hematology/Oncology, Cooper University Hospital, Camden, USA.

A 58-year-old male with the chronic phase of chronic myeloid leukemia (CML), treated with a tyrosine kinase inhibitor (TKI), bosutinib, since the past two years, presented with bright red bleeding per rectum and disseminated intravascular coagulation. A bone marrow biopsy reverse transcription-polymerase chain reaction revealed a promyelocytic blast crisis, with leukemic cells displaying both  and α chimeric genes. Cytogenetic studies revealed translocations of both t(15;17) and t(9;22). Read More

Cancers (Basel) 2020 Apr 7;12(4). Epub 2020 Apr 7.

Department of Biology, Faculty of Medicine and Dentistry, Palacky University, 77515 Olomouc, Czech Republic.

Inflammatory and oncogenic signaling, both known to challenge genome stability, are key drivers of -positive chronic myeloid leukemia (CML) and V617F-positive chronic myeloproliferative neoplasms (MPNs). Despite similarities in chronic inflammation and oncogene signaling, major differences in disease course exist. Although BCR-ABL has robust transformation potential, V617F-positive polycythemia vera (PV) is characterized by a long and stable latent phase. Read More

Biomark Med 2020 Apr 9;14(6):451-458. Epub 2020 Apr 9.

Department of Hematology, Iuliu Hatieganu University of Medicine & Pharmacy, 21 December Boulevard, 400124, Cluj-Napoca, Romania.

Chronic myelogenous leukemia (CML) is a hematological malignancy characterized by the excessive proliferation of myeloid progenitors. In the case of CML, these extracellular vesicles (EVs) were shown to communicate with hematopoietic stem cells, mesenchymal stem cells, myeloid derived suppressor cells and endothelial cells determining a beneficial microenvironment for the CML clone. Moreover, as these EVs are marked through BCR-ABL1, they were shown to be useful in clinical research in determining the grade of molecular remission with further studies being needed to determine if they are better or worse at predicting CML relapse. Read More

Blood 2020 Apr 8. Epub 2020 Apr 8.

BC Cancer Research Centre, Vancouver, Canada.

Overcoming drug resistance and targeting cancer stem cells remain challenges for curative cancer treatment. To investigate the role of miRNAs in regulating drug resistance and leukemic stem cell (LSCs) fate, we performed global transcriptome profiling in treatment-naïve chronic myeloid leukemia (CML) stem/progenitor cells and identified that miR-185 levels anticipate their response to ABL tyrosine kinase inhibitors (TKIs). miR-185 functions as a tumor suppressor; its restored expression impaired survival of drug-resistant cells, sensitized them to TKIs in vitro, and markedly eliminated long-term repopulating LSCs and infiltrating blast cells, conferring a survival advantage in pre-clinical xenotransplantation models. Read More

Ann Hematol 2020 May 6;99(5):991-1006. Epub 2020 Apr 6.

Department of Hematology and Oncology, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Separase, a cysteine endopeptidase, is a key player in mitotic sister chromatid separation, replication fork dynamics, and DNA repair. Aberrant expression and/or altered separase proteolytic activity are associated with aneuploidy, tumorigenesis, and disease progression. Since genomic instability and clonal evolution are hallmarks of progressing chronic myeloid leukemia (CML), we have comparatively examined separase proteolytic activity in TKI-treated chronic phase CML. Read More