- Chronic myelogenous leukemia, is defined by the presence of the Philadelphia chromosome; a reciprocal translocation occurs between chromosomes 9 and 22, leading to the new oncogeneic BCR::ABL1 gene1
- The resulting BCR::ABL1 fusion gene produces a constitutively active tyrosine kinase that promotes abnormal myeloid cell proliferation2
Explore the pathophysiology, epidemiology, and diagnostic criteria of CML
Getting CML under control
Potential to attempt TFR5
Improve survival5
Achieve and maintain milestones6
Prevent disease progression6
Preserving/Improving QOL
Improve or maintain QOL5
Minimize treatment-related toxicities7
Treatment goals are focused on controlling CML pathology while preserving/improving QOL
Milestones That Matter!
European LeukemiaNet 2025 recommendations
Molecular monitoring is important for determining whether patients are responding well to therapy8
Long-term efficacy decreases with successive treatments and is linked with reduced survival9
In CML, for patients treated with a second line and a third line and those beyond TKI, the OS in 5 years decreased to 82% and 77%, respectively (p = 0.01).
ABL1, Abelson tyrosine kinase 1; BCR, breakpoint cluster region; CML, chronic myeloid leukemia; ASIR, age-standardized incidence rate; ASDR, age standardized death rate; TKI, Tyrosine kinase inhibitor; OS, overall survival; QOL, Quality of life; TFR, Treatment free remission; MMR, major molecular response (BCR::ABL1IS ≤0.1%); ACA, additional chromosome abnormalities in Ph+ cells; BCR, breakpoint cluster region; ELN, European LeukemiaNet; ELTS, European Treatment Outcome Study Long-Term Survival; IS, International
References
Sampaio MM, Santos ML, Marques HS, de Souza Gonçalves VL, Araújo GR, Lopes LW, Apolonio JS, Silva CS, de Sá Santos LK, Cuzzuol BR, Guimarães QE. Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review. World journal of clinical oncology. 2021 Feb 24;12(2):69.
Huang TT, Wang X, Qiang SJ, Zhao ZN, Wu ZX, Ashby Jr CR, Li JZ, Chen ZS. The discovery of novel BCR-ABL tyrosine kinase inhibitors using a pharmacophore modeling and virtual screening approach. Frontiers in Cell and Developmental Biology. 2021 Mar 4;9:649434.
National Cancer Institute (NCI). Philadelphia chromosome. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/philadelphia-chromosome . Last accessed 10/9/2025
Choi EJ. Asciminib: the first-in-class allosteric inhibitor of BCR:: ABL1 kinase. Blood research. 2023 Apr 30;58(S1):S29-36.
Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, Clark RE, Cortes JE, Deininger MW, Guilhot F, Hjorth-Hansen H. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020 Apr;34(4):966-84
National Comprehensive Cancer Network® (NCCN®), NCCN Guidelines Version 1.2026 Chronic Myeloid Leukemia. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf . Last accessed 10/9/2025
Khoury HJ, Williams LA, Atallah E, Hehlmann R. Chronic myeloid leukemia: what every practitioner needs to know in 2017. American Society of Clinical Oncology Educational Book. 2017 Jan 1;37:468-79
Apperley JF, Milojkovic D, Cross NC, Hjorth-Hansen H, Hochhaus A, Kantarjian H, Lipton JH, Malhotra H, Niederwieser D, Radich J, Rousselot P. 2025 European LeukemiaNet recommendations for the management of chronic myeloid leukemia: CHRONIC MYELOID LEUKEMIA. Leukemia. 2025 Jul 11:1-7.
Bosi GR, Fogliatto LM, Costa TE, Grokoski KC, Pereira MP, Bugs N, Kalil M, Fraga C, Daudt LE, Silla LM. What happens to intolerant, relapsed or refractory chronic myeloid leukemia patients without access to clinical trials?. Hematology, Transfusion and Cell Therapy. 2019 Oct 10;41:222-8.
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