Abstract
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype with a poor prognosis under conventional chemotherapy. Ph-like ALL has a similar gene expression profile to Philadelphia chromosome-positive (Ph+) ALL, but is highly heterogeneous in terms of genomic alterations. Approximately 10–20% of patients with Ph-like ALL harbor ABL class (e.g. ABL1, ABL2, PDGFRB, and CSF1R) rearrangements. Additional genes that form fusion genes with ABL class genes are still being researched. These aberrations result from rearrangements including chromosome translocations or deletions and may be targets of tyrosine kinase inhibitors (TKIs). However, due to the heterogeneity and rarity of each fusion gene in clinical practice, there is limited data on the efficacy of tyrosine kinase inhibitors. Here, we report three cases of Ph-like B-ALL with ABL1 rearrangements treated with the dasatinib backbone for the CNTRL::ABL1, LSM14A::ABL1, and FOXP1::ABL1 fusion genes. All three patients achieved rapid and profound remission with no significant adverse events. Our findings suggest that dasatinib is a potent TKI for the treatment of ABL1-rearranged Ph-like ALL and can be used as a first-line treatment option for such patients.
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The data supporting this study’s findings are available from the corresponding author upon reasonable request.
References
Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D et al (2014) Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 371(11):1005–1015. https://doi.org/10.1056/NEJMoa1403088
Chiaretti S, Messina M, Della Starza I, Piciocchi A, Cafforio L, Cavalli M et al (2021) Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913. Haematologica 106(6):1559–1568. https://doi.org/10.3324/haematol.2020.247973
Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X et al (2012) Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell 22(2):153–166. https://doi.org/10.1016/j.ccr.2012.06.005
Ernst T, Score J, Deininger M, Hidalgo-Curtis C, Lackie P, Ershler WB et al (2011) Identification of FOXP1 and SNX2 as novel ABL1 fusion partners in acute lymphoblastic leukaemia. Br J Haematol 153(1):43–46. https://doi.org/10.1111/j.1365-2141.2010.08457.x
Ma X, Liu Y, Liu Y, Alexandrov LB, Edmonson MN, Gawad C et al (2018) Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Nature 555(7696):371–376. https://doi.org/10.1038/nature25795
Biloglav A, Olsson-Arvidsson L, Theander J, Behrendtz M, Castor A, Johansson B (2020) SFPQ-ABL1-positive B-cell precursor acute lymphoblastic leukemias. Genes Chromosomes Cancer 59(9):540–543. https://doi.org/10.1002/gcc.22852
Reshmi SC, Harvey RC, Roberts KG, Stonerock E, Smith A, Jenkins H et al (2017) Targetable kinase gene fusions in high-risk B-ALL: a study from the Children’s Oncology Group. Blood 129(25):3352–3361. https://doi.org/10.1182/blood-2016-12-758979
Hsu YC, Yu CH, Chen YM, Roberts KG, Ni YL, Lin KH et al (2021) Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan. Sci Rep 11(1):5802. https://doi.org/10.1038/s41598-021-85213-6
Papenhausen P, Kelly CA, Zhang Z, Tepperberg J, Burnside RD, Schwartz S (2019) Multidisciplinary analysis of pediatric T-ALL: 9q34 gene fusions. Cancer Genet 231-232:1–13. https://doi.org/10.1016/j.cancergen.2018.12.002
Kakadia PM, Tizazu B, Mellert G, Harbott J, Rottgers S, Quentmeier H et al (2011) A novel ABL1 fusion to the SH2 containing inositol phosphatase-1 (SHIP1) in acute lymphoblastic leukemia (ALL). Leukemia 25(10):1645–1649. https://doi.org/10.1038/leu.2011.129
Tanasi I, Ba I, Sirvent N, Braun T, Cuccuini W, Ballerini P et al (2019) Efficacy of tyrosine kinase inhibitors in Ph-like acute lymphoblastic leukemia harboring ABL-class rearrangements. Blood 134(16):1351–1355. https://doi.org/10.1182/blood.2019001244
US Department of Health and Human Services (2021) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Published: November 27. US Department of Health and Human Services National Institutes of Health National Cancer Institute
Kantarjian H, Thomas D, O’Brien S, Cortes J, Giles F, Jeha S et al (2004) Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101(12):2788–2801. https://doi.org/10.1002/cncr.20668
Yenamandra AK, Kaviany S, Borinstein SC, Friedman DL, Kovach AE (2019) BCR-ABL1-like B-Lymphoblastic leukemia/Lymphoma with FOXP1-ABL1 rearrangement: comprehensive laboratory identification allowing tyrosine kinase inhibitor use. Lab Med 50(4):401–405. https://doi.org/10.1093/labmed/lmz008
Tran TH, Harris MH, Nguyen JV, Blonquist TM, Stevenson KE, Stonerock E et al (2018) Prognostic impact of kinase-activating fusions and IKZF1 deletions in pediatric high-risk B-lineage acute lymphoblastic leukemia. Blood Adv 2(5):529–533. https://doi.org/10.1182/bloodadvances.2017014704
Zheng J, Wu S, Hu Y, Gao L, Ling J, Lu Q et al (2021) Management of ETV6-ABL1-positive childhood acute lymphoblastic leukaemia: report of two cases, a literature review and a call for action. Br J Haematol 193(1):197–200. https://doi.org/10.1111/bjh.17271
Aldoss I, Pullarkat V (2019) Response to single agent dasatinib post allogeneic transplant in B-cell acute lymphoblastic leukemia with NUP214-ABL1. Leuk Lymphoma 60(11):2832–2834. https://doi.org/10.1080/10428194.2019.1605510
Eyre T, Schwab CJ, Kinstrie R, McGuire AK, Strefford J, Peniket A et al (2012) Episomal amplification of NUP214-ABL1 fusion gene in B-cell acute lymphoblastic leukemia. Blood 120(22):4441–4443. https://doi.org/10.1182/blood-2012-09-456517
Jabbour E, Short NJ, Ravandi F, Huang X, Daver N, DiNardo CD et al (2018) Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study. Lancet Haematol 5(12):e618–e627. https://doi.org/10.1016/S2352-3026(18)30176-5
Chiaretti S, Messina M, Grammatico S, Piciocchi A, Fedullo AL, Di Giacomo F et al (2018) Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications. Br J Haematol 181(5):642–652. https://doi.org/10.1111/bjh.15251
Jabbour E, Patel K, Jain N, Duose D, Luthra R, Short NJ et al (2021) Impact of Philadelphia chromosome-like alterations on efficacy and safety of blinatumomab in adults with relapsed/refractory acute lymphoblastic leukemia: a post hoc analysis from the phase 3 TOWER study. Am J Hematol 96(10):E379–E383. https://doi.org/10.1002/ajh.26281
Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K et al (2017) Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood 129(25):3322–3331. https://doi.org/10.1182/blood-2017-02-769208
Funding
This work was supported by the grants from the National Key R&D Program of China (2022YFC2502703), National Natural Science Foundation of China (grant nos. 81970138 and 82270165), Jiangsu Province Natural Science Foundation of China (grant no. BK20221235), Translational Research Grant of NCRCH (grant no. 2020ZKMB05), Jiangsu Province “333” Project, Social Development Project of the Science and Technology Department of Jiangsu (grant no. BE2021649), Gusu Key Medical Talent Program (grant no. GSWS2019007), and Bethune Charitable Foundation (BCF-IBW-XY-20220930-08).
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Kai-Wen Tan and Yi-Yan Zhu were responsible for protocol writing, data analysis, and manuscript writing. Qiao-Cheng Qiu, Man Wang, and Hong-Jie Shen acquired and processed patient specimens. Si-Man Huang, Han-Yu Cao, Chao-Ling Wan, and Yan-Yan Li were responsible for data extraction. Hai-Ping Dai and Sheng-Li Xue helped perform the analysis with constructive discussions. The submission has been read and approved for submission by all authors.
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This case study involving human participants was in accordance with the ethical standards of the Ethics Committee of the First Affiliated Hospital of Soochow University.
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Tan, KW., Zhu, YY., Qiu, QC. et al. Rapid molecular response to dasatinib in Ph-like acute lymphoblastic leukemia patients with ABL1 rearrangements: case series and literature review. Ann Hematol 102, 2397–2402 (2023). https://doi.org/10.1007/s00277-023-05236-z
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DOI: https://doi.org/10.1007/s00277-023-05236-z