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Cancer Res 2022 May 31. Epub 2022 May 31.

Stanford University, Stanford University, CA, United States.

Small molecule Tyrosine Kinase Inhibitors (TKIs) have revolutionized cancer treatment and greatly improved patient survival. However, life-threatening cardiotoxicity of many TKIs has become a major concern. Ponatinib (ICLUSIG) was developed as an inhibitor of the BCR-ABL oncogene and is among the most cardiotoxic of TKIs. Read More

Front Oncol 2022 8;12:904510. Epub 2022 Jun 8.

Department of Medicine, General Pathology Section, University of Verona, Verona, Italy.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the acquisition of t(9;22) generating the fusion tyrosine kinase BCR::ABL1. However, despite the crucial role of this protein in the dysregulation of numerous signal transduction pathways, a direct measure of BCR::ABL1 kinase activity in chronic phase (CP) CML was never accomplished due to intense degradative activity present in mature leukocytes. Therefore, we developed a procedure suitable to preserve BCR::ABL1 protein under non-denaturing, neutral pH conditions in primary, chronic phase (CP)-CML samples. Read More

Front Oncol 2022 8;12:921587. Epub 2022 Jun 8.

Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Introduction: The hematological manifestations of corona virus disease 2019 (COVID-19) can confound the diagnosis and therapy of other diseases. In this paper, we firstly reported a case of chronic myeloid leukemia (CML) of delayed diagnosis and intolerance to tyrosine kinase inhibitors (TKIs) concurrent with COVID-19.

Case Presentation: A 56-year-old female was diagnosed as COVID-19 with no obvious leukocytosis [white blood cell (WBC), ≤17 × 10/L] or splenomegaly until ablation of the virus. Read More

Blood Cancer J 2022 Jun 24;12(6):94. Epub 2022 Jun 24.

Hematology Department, Hospital 12 de Octubre, Complutense University, CNIO, Madrid, Spain.

Int J Mol Sci 2022 Jun 7;23(12). Epub 2022 Jun 7.

Departamento de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain.

Chronic myeloid leukaemia (CML) is a haematological neoplasm driven by the fusion oncogene. The monogenic aspect of the disease and the feasibility of ex vivo therapies in haematological disorders make CML an excellent candidate for gene therapy strategies. The ability to abolish any coding sequence by CRISPR-Cas9 nucleases offers a powerful therapeutic opportunity to CML patients. Read More

Genes (Basel) 2022 May 26;13(6). Epub 2022 May 26.

Clinical Pathology Department, Tanta University, Tanta 31527, Egypt.

Introduction: The prognosis of chronic myeloid leukemia (CML) patients has been dramatically improved with the introduction of imatinib (IM), the first tyrosine kinase inhibitor (TKI). TKI resistance is a serious problem in IM-based therapy. The human S-phase kinase-associated protein 2 () gene may play an essential role in the genesis and progression of CML. Read More

Oncol Rep 2022 Aug 22;48(2). Epub 2022 Jun 22.

Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig‑Holstein, Campus Kiel, D-24105 Kiel, Germany.

Although chronic myeloid leukemia (CML) can be effectively treated using BCR‑ABL1 kinase inhibitors, resistance due to kinase alterations or to BCR‑ABL1 independent mechanisms remain a therapeutic challenge. For the latter, the underlying mechanisms are widely discussed; for instance, gene expression changes, epigenetic factors and alternative signaling pathway activation. In the present study, ‑CML cell models of resistance against the tyrosine kinase inhibitors (TKIs) imatinib (0. Read More

Br J Haematol 2022 Jun 21. Epub 2022 Jun 21.

Department of Haematology, Royal Adelaide Hospital and SA Pathology, Adelaide, South Australia, Australia.

Recent approval of asciminib, a novel "specifically targeting the ABL myristoyl pocket" (STAMP) BCR-ABL1 inhibitor, for the treatment of chronic myeloid leukaemia (CML) patients who have either failed ≥2 lines of therapy or have the T315I mutation, has provided clinicians with a wider selection of potentially effective treatment options. Asciminib has the attractive twin attributes of high potency directed against BCR-ABL1 and good tolerability based on its limited off-target effects. However, it is unclear exactly where asciminib will be positioned amongst the other available tyrosine kinase inhibitors (TKIs), especially ponatinib which is also available for the same indications. Read More

Front Pharmacol 2022 20;13:809551. Epub 2022 May 20.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.

Chronic myeloid leukemia (CML) accounts for a major cause of death in adult leukemia patients due to mutations or other reasons for dysfunction in the ABL proto-oncogene. The ubiquitous BCR-ABL expression stimulates CML by activating CDK1 and cyclin B1, promoting pro-apoptotic, and inhibiting antiapoptotic marker expression along with regulations in RAS pathway activation. Thus, inhibitors of cyclins and the RAS pathway by ERK are of great interest in antileukemic treatments. Read More

Med Oncol 2022 Jun 18;39(9):126. Epub 2022 Jun 18.

Department of Medical Biology, Faculty of Medicine, Ege University, Bornova, 35100, Izmir, Turkey.

Chronic myeloid leukemia (CML) is a myeloproliferative disease that mediated by BCR/ABL oncogenic signaling. CML can be targeted with the imatinib, dasatinib, and nilotinib TKI inhibitors, the latter two of them have been approved for imatinib-resistant or -intolerant CML patients. The TKIs resistance occurs by different molecular mechanisms, including overexpression of BCR-ABL, mutations in the TKI binding site of BCR/ABL, and ER-stress. Read More

Medicine (Baltimore) 2022 Jun 17;101(24):e29179. Epub 2022 Jun 17.

Department of Hematology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China.

Rationale: Persistent leukocytosis with megalosplenia is a common manifestation among patients with myeloproliferative neoplasm (MPN), especially for chronic myeloid leukemia (CML) patients. Here, we report a rare case of myeloid neoplasm with BCR-PDGFRA rearrangement characterized by obvious elevation of leukocyte count and megalosplenia.

Patient Concerns: A 32-year-old man presented with persistent leukocytosis and megalosplenia. Read More

Biomol Ther (Seoul) 2022 Jun 15. Epub 2022 Jun 15.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. Read More

Zhonghua Yi Xue Za Zhi 2022 May;102(20):1523-1529

Department of Hematology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China.

To explore the related factors affecting the outcome of treatment free remission (TFR) in patients with chronic myeloid leukemia (CML). Clinical data of CML patients with automatic discontinuation of tyrosine kinase inhibitor (TKI) from the CML cooperative organization of Henan province between June 2, 2013 to March 27, 2021 and the follow-up time was ≥ 6 months were retrospectively analyzed. Log-rank test was used for univariate analysis and Cox proportional risk regression model was used for multivariate analysis. Read More

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2022 Jun;30(3):677-687

Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu 610000, Sichuan Province, China,E-mail:

Objective: To investigate the effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. Read More

Zhonghua Xue Ye Xue Za Zhi 2022 May;43(5):436-440

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

Clin Case Rep 2022 Jun 5;10(6):e05919. Epub 2022 Jun 5.

Hematology and Transplant Center University Hospital "San Giovanni di Dio e Ruggi d'Aragona" Salerno Italy.

Kaposi's sarcoma is associated with immunosuppression and human herpesvirus 8 infection, while rarely described in myeloid malignancies. Here, we illustrate a rare case of chronic myeloid leukemia treated with imatinib, a tyrosine kinase inhibitor, who developed a human herpesvirus 8-related Kaposi's sarcoma. Read More

Cell Metab 2022 Jun;34(6):801-802

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.

In this issue of Cell Metabolism, Liu et al. demonstrate that Prmt7 can regulate the onset and progression of leukemogenesis by inhibiting self-renewal capacity of leukemic stem cells (LSCs) as modeled in a murine version of chronic myeloid leukemia (CML). Read More

Cell Stress Chaperones 2022 Jun 8. Epub 2022 Jun 8.

Key Laboratory of Laboratory Medical Diagnostics Designated By the Ministry of Education, Department of Clinical Hematology, Chongqing Medical University, Chongqing, China.

Chronic myeloid leukemia (CML) is a hematological tumor marked by the bcr-abl fusion gene formed by t (9;22) (q34; q11), which translated into the BCR-ABL protein. Tyrosine kinase inhibitors (TKIs) have been widely used to cure CML patients. Nevertheless, the emergence of TKI resistance has become the problem to the outcome of CML patients. Read More

Exp Hematol Oncol 2022 Jun 7;11(1):36. Epub 2022 Jun 7.

Department of Clinical Laboratory, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Background: Tyrosine kinase inhibitors have achieved quite spectacular advances in the treatment of chronic myeloid leukemia (CML), but disease progression and drug resistance that related to the T315I mutation, remain major obstacles. Dendritic cell-derived exosomes (Dex) induce NK cell immunity, but have yet to achieve satisfactory clinical efficacy. An approach to potentiate antitumor immunity by inducing both NK- and T-cell activation is urgently needed. Read More

Drug Des Devel Ther 2022 30;16:1595-1604. Epub 2022 May 30.

Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Background: Imatinib is used to treat chronic myelogenous leukemia (CML). Variations in imatinib pharmacokinetics have been linked to genetic variations. That has an impact on imatinib response and adverse effects. Read More

Am Soc Clin Oncol Educ Book 2022 Apr;42:1-19

Global Oncology Program and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

The 1960 discovery of the Philadelphia chromosome in chronic myeloid leukemia (CML) marked the beginning of the modern genomic era of oncology. In the following years, the molecular underpinnings of CML were unraveled, culminating in the development of the first molecularly targeted therapy: imatinib. Imatinib revolutionized CML management, inducing deep molecular responses for most patients and aligning survival curves with those of age-matched control participants. Read More

Hematol Transfus Cell Ther 2022 May 3. Epub 2022 May 3.

Complexo Hospital de Clínicas, Universidade Federal do Paraná (CHC-UFPR), Curitiba, PR, Brazil.

Introduction: Treatment-free remission (TFR) is a new goal of chronic myeloid leukemia (CML) therapy. TFR is feasible when the patient has achieved a deep and stable molecular response and met the criteria required to ensure its success. Treatment discontinuation should not be proposed to the CML patient if minimum conditions are not met. Read More

Biophys J 2022 Jun 31;121(12):2251-2265. Epub 2022 May 31.

Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, Maryland; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

BCR-ABL drives chronic myeloid leukemia (CML). BCR binding to GRB2 transduces signaling via the Ras/MAPK pathway. Despite considerable data confirming the binding, molecular-level understanding of exactly how the two proteins interact, and, especially, what are the determinants of the specificity of the SH2 domain-phosphorylated BCR (pBCR) recognition are still open questions. Read More

Exp Cell Res 2022 Aug 26;417(2):113219. Epub 2022 May 26.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan. Electronic address:

Induction of differentiation sensitizes chronic myeloid leukemia (CML) cells to the BCR-ABL inhibitor imatinib by mechanisms that remain unknown. We previously identified the BCR-ABL downstream effector CD69 which inhibits imatinib-induced CML cell differentiation. Herein, we found that the erythroid differentiation inducers activin A and aclacinomycin A induced expression of erythroid markers (α-globin, ζ-globin, GATA-1, and glycophorin A) and simultaneously reduced CD69 levels in K562 CML cells. Read More

Angew Chem Int Ed Engl 2022 May 31:e202202770. Epub 2022 May 31.

Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Phosphorylation-inducing chimeric small molecules (PHICS) can enable a kinase to act at a new cellular location or phosphorylate non-native substrates (neo-substrates)/ sites (neo-phosphorylations). We report a modular design and high-yielding synthesis of such PHICS that endowed multiple new activities to protein kinase C (PKC). For example, while PKC is unable to downregulate the activity of a gain-of-function variant (S180A) of Bruton's tyrosine kinase that evokes B cell malignancy phenotype, PHICS enabled PKC to induce inhibitory neo-phosphorylations on this variant. Read More

Oncologist 2022 03;27(2):149-157

Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.

On December 18, 2020, US Food and Drug Administration (FDA) approved a supplemental application for ponatinib extending the indication in patients with chronic-phase chronic myeloid leukemia (CP-CML) to patients with resistance or intolerance of at least 2 prior kinase inhibitors. Ponatinib was initially approved in December 2012 but was briefly voluntarily withdrawn due to serious safety concerns including the risk of arterial occlusive events (AOE). It returned to the market in December 2013 with an indication limited to patients with T315I mutation or for whom no other tyrosine kinase inhibitor (TKI) therapy was indicated with revised warnings and precautions. Read More

Molecules 2022 May 18;27(10). Epub 2022 May 18.

Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.

This paper reports on a novel series of tyrosine kinase inhibitors (TKIs) potentially useful for the treatment of chronic myeloid leukemia (CML). The newly designed and synthesized compounds are structurally related to nilotinib (NIL), a second-generation oral TKI, and to a series of imatinib (IM)-based TKIs, previously reported by our research group, these latter characterized by a hybrid structure between TKIs and heme oxygenase-1 (HO-1) inhibitors. The enzyme HO-1 was selected as an additional target since it is overexpressed in many cases of drug resistance, including CML. Read More

Cancers (Basel) 2022 May 21;14(10). Epub 2022 May 21.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

The most recent two decades have seen tremendous progress in the understanding and treatment of chronic myeloid leukemia, a disease defined by the characteristic Philadelphia chromosome and the ensuing BCR::ABL fusion protein. However, the biology of the disease extends beyond the Philadelphia chromosome into a nebulous arena of chromosomal and genetic instability, which makes it a genetically heterogeneous disease. The BCR::ABL oncoprotein creates a fertile backdrop for oxidative damage to the DNA, along with impairment of genetic surveillance and the favoring of imprecise error-prone DNA repair pathways. Read More

Exp Hematol Oncol 2022 May 27;11(1):33. Epub 2022 May 27.

Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

Background: With the widespread clinical application of tyrosine kinase inhibitors (TKIs), an increasing number of chronic myeloid leukaemia (CML) patients have developed resistance or intolerance to TKIs. BCR/ABL is the oncoprotein of CML. HSP90 is an essential chaperone of BCR/ABL and plays an important role in protein folding and the function of BCR/ABL. Read More

MicroPubl Biol 2022 13;2022. Epub 2022 Apr 13.

Department of Experimental Pathology and Immunology, Faculty of Medicine, American University of Beirut, Lebanon.