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Both the subtypes of KIT mutation and minimal residual disease are associated with prognosis in core binding factor acute myeloid leukemia: a retrospective clinical cohort study in single center

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Abstract

Core binding factor acute myeloid leukemia (CBF-AML), including cases with KIT mutation, is currently defined as a low-risk AML. However, some patients have poor response to treatment, and the prognostic significance of KIT mutation is still controversial. This study aimed to explore the prognostic significance of different KIT mutation subtypes and minimal residual disease (MRD) in CBF-AML. We retrospectively evaluated continuous patients diagnosed with CBF-AML in our center between January 2014 and April 2019. Of the 215 patients, 147 (68.4%) and 68 (31.6%) patients were RUNX1-RUNX1T1- and CBFB-MYH11 positive, respectively. KIT mutations were found in 71 (33.0%) patients; of them, 38 (53.5%) had D816/D820 mutations. After excluding 10 patients who died or were lost to follow-up within a half year, 42.0% (n = 86) of the remaining 205 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). An MRD > 0.1% at the end of two cycles of consolidation predicted relapse (P < 0.001). Multivariate analysis showed that D816 or D820 mutations and MRD > 0.1% at the end of two cycles of consolidation were independent adverse factors affecting relapse-free survival (RFS) and overall survival (OS). Allo-HSCT could improve RFS (74.4% vs. 34.6%, P < 0.001) and OS (78.1% vs. 52.3%, P = 0.002). In conclusion, high-risk CBF-AML patients must be identified before treatment. D816/D820 mutation, MRD > 0.1% at the end of two cycles of consolidation chemotherapy predicted poor survivals, and allo-HSCT can improve the survival of properly identified patients.

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References

  1. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A (1998) The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 92(7):2322–2333

    Article  CAS  Google Scholar 

  2. Byrd JC, Mrózek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, Koduru PR, Moore JO, Stone RM, Mayer RJ, Feldman EJ, Davey FR, Schiffer CA, Larson RA, Bloomfield CD (2002) Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 100(13):4325–4336. https://doi.org/10.1182/blood-2002-03-0772

    Article  CAS  PubMed  Google Scholar 

  3. Prébet T, Boissel N, Reutenauer S, Thomas X, Delaunay J, Cahn JY, Pigneux A, Quesnel B, Witz F, Thépot S, Ugo V, Terre C, Recher C, Tavernier E, Hunault M, Esterni B, Castaigne S, Guilhot F, Dombret H, Vey N (2009) Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML intergroup. J Clin Oncol 27(28):4747–4753. https://doi.org/10.1200/jco.2008.21.0674

    Article  PubMed  Google Scholar 

  4. Paschka P, Marcucci G, Ruppert AS, Mrózek K, Chen H, Kittles RA, Vukosavljevic T, Perrotti D, Vardiman JW, Carroll AJ, Kolitz JE, Larson RA, Bloomfield CD (2006) Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a cancer and leukemia group B study. J Clin Oncol 24(24):3904–3911. https://doi.org/10.1200/jco.2006.06.9500

    Article  CAS  PubMed  Google Scholar 

  5. Boissel N, Leroy H, Brethon B, Philippe N, de Botton S, Auvrignon A, Raffoux E, Leblanc T, Thomas X, Hermine O, Quesnel B, Baruchel A, Leverger G, Dombret H, Preudhomme C (2006) Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia 20(6):965–970. https://doi.org/10.1038/sj.leu.2404188

    Article  CAS  PubMed  Google Scholar 

  6. Jourdan E, Boissel N, Chevret S, Delabesse E, Renneville A, Cornillet P, Blanchet O, Cayuela JM, Recher C, Raffoux E, Delaunay J, Pigneux A, Bulabois CE, Berthon C, Pautas C, Vey N, Lioure B, Thomas X, Luquet I, Terré C, Guardiola P, Béné MC, Preudhomme C, Ifrah N, Dombret H (2013) Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood 121(12):2213–2223. https://doi.org/10.1182/blood-2012-10-462879

    Article  CAS  PubMed  Google Scholar 

  7. Qin YZ, Zhu HH, Jiang Q, Xu LP, Jiang H, Wang Y, Zhao XS, Liu YR, Zhang XH, Liu KY, Huang XJ (2018) Heterogeneous prognosis among KIT mutation types in adult acute myeloid leukemia patients with t(8;21). Blood Cancer J 8(8):76. https://doi.org/10.1038/s41408-018-0116-1

    Article  PubMed  PubMed Central  Google Scholar 

  8. Duan W, Liu X, Jia J, Wang J, Gong L, Jiang Q, Zhao T, Wang Y, Zhang X, Xu L, Zhao X, Qin Y, Shi H, Chang Y, Huang X, Jiang H (2020) The loss or absence of minimal residual disease of <0·1% at any time after two cycles of consolidation chemotherapy in CBFB-MYH11-positive acute myeloid leukaemia indicates poor prognosis. Br J Haematol. https://doi.org/10.1111/bjh.16745

  9. Qin YZ, Xu LP, Chen H, Jiang Q, Wang Y, Jiang H, Zhang XH, Han W, Chen YH, Wang FR, Wang JZ, Zhu HH, Liu YR, Jiang B, Liu KY, Huang XJ (2015) Allogeneic stem cell transplant may improve the outcome of adult patients with inv(16) acute myeloid leukemia in first complete remission with poor molecular responses to chemotherapy. Leuk Lymphoma 56(11):3116–3123. https://doi.org/10.3109/10428194.2015.1032964

    Article  CAS  PubMed  Google Scholar 

  10. Zhu HH, Zhang XH, Qin YZ, Liu DH, Jiang H, Chen H, Jiang Q, Xu LP, Lu J, Han W, Bao L, Wang Y, Chen YH, Wang JZ, Wang FR, Lai YY, Chai JY, Wang LR, Liu YR, Liu KY, Jiang B, Huang XJ (2013) MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial. Blood 121(20):4056–4062. https://doi.org/10.1182/blood-2012-11-468348

    Article  CAS  PubMed  Google Scholar 

  11. Lv M, Wang Y, Chang YJ, Zhang XH, Xu LP, Jiang Q, Jiang H, Lu J, Chen H, Han W, Wang FR, Wang JZ, Chen Y, Yan CH, Zhang YY, Sun YQ, Mo XD, Zhu HH, Jia JS, Zhao T, Wang J, Liu KY, Huang XJ (2019) Myeloablative haploidentical transplantation Is superior to chemotherapy for patients with intermediate-risk acute myelogenous leukemia in first complete remission. Clin Cancer Res 25(6):1737–1748. https://doi.org/10.1158/1078-0432.Ccr-18-1637

    Article  CAS  PubMed  Google Scholar 

  12. Qin YZ, Zhu HH, Jiang Q, Jiang H, Zhang LP, Xu LP, Wang Y, Liu YR, Lai YY, Shi HX, Jiang B, Huang XJ (2014) Prevalence and prognostic significance of c-KIT mutations in core binding factor acute myeloid leukemia: a comprehensive large-scale study from a single Chinese center. Leuk Res 38(12):1435–1440. https://doi.org/10.1016/j.leukres.2014.09.017

    Article  CAS  PubMed  Google Scholar 

  13. Cairoli R, Beghini A, Turrini M, Bertani G, Nadali G, Rodeghiero F, Castagnola C, Lazzaroni F, Nichelatti M, Ferrara F, Pizzolo G, Pogliani E, Rossi G, Martinelli G, Morra E (2013) Old and new prognostic factors in acute myeloid leukemia with deranged core-binding factor beta. Am J Hematol 88(7):594–600. https://doi.org/10.1002/ajh.23461

    Article  CAS  PubMed  Google Scholar 

  14. Schnittger S, Kohl TM, Haferlach T, Kern W, Hiddemann W, Spiekermann K, Schoch C (2006) KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood 107(5):1791–1799. https://doi.org/10.1182/blood-2005-04-1466

    Article  CAS  PubMed  Google Scholar 

  15. Duployez N, Marceau-Renaut A, Boissel N, Petit A, Bucci M, Geffroy S, Lapillonne H, Renneville A, Ragu C, Figeac M, Celli-Lebras K, Lacombe C, Micol JB, Abdel-Wahab O, Cornillet P, Ifrah N, Dombret H, Leverger G, Jourdan E, Preudhomme C (2016) Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood 127(20):2451–2459. https://doi.org/10.1182/blood-2015-12-688705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cairoli R, Beghini A, Grillo G, Nadali G, Elice F, Ripamonti CB, Colapietro P, Nichelatti M, Pezzetti L, Lunghi M, Cuneo A, Viola A, Ferrara F, Lazzarino M, Rodeghiero F, Pizzolo G, Larizza L, Morra E (2006) Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood 107(9):3463–3468. https://doi.org/10.1182/blood-2005-09-3640

    Article  CAS  PubMed  Google Scholar 

  17. Kim HJ, Ahn HK, Jung CW, Moon JH, Park CH, Lee KO, Kim SH, Kim YK, Kim HJ, Sohn SK, Kim SH, Lee WS, Kim KH, Mun YC, Kim H, Park J, Min WS, Kim HJ, Kim DH (2013) KIT D816 mutation associates with adverse outcomes in core binding factor acute myeloid leukemia, especially in the subgroup with RUNX1/RUNX1T1 rearrangement. Ann Hematol 92(2):163–171. https://doi.org/10.1007/s00277-012-1580-5

    Article  CAS  PubMed  Google Scholar 

  18. Yui S, Kurosawa S, Yamaguchi H, Kanamori H, Ueki T, Uoshima N, Mizuno I, Shono K, Usuki K, Chiba S, Nakamura Y, Yanada M, Kanda J, Tajika K, Gomi S, Fukunaga K, Wakita S, Ryotokuji T, Fukuda T, Inokuchi K (2017) D816 mutation of the KIT gene in core binding factor acute myeloid leukemia is associated with poorer prognosis than other KIT gene mutations. Ann Hematol 96(10):1641–1652. https://doi.org/10.1007/s00277-017-3074-y

    Article  CAS  PubMed  Google Scholar 

  19. Yin JA, O'Brien MA, Hills RK, Daly SB, Wheatley K, Burnett AK (2012) Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial. Blood 120(14):2826–2835. https://doi.org/10.1182/blood-2012-06-435669

    Article  CAS  PubMed  Google Scholar 

  20. Ishikawa Y, Kawashima N, Atsuta Y, Sugiura I, Sawa M, Dobashi N, Yokoyama H, Doki N, Tomita A, Kiguchi T, Koh S, Kanamori H, Iriyama N, Kohno A, Moriuchi Y, Asada N, Hirano D, Togitani K, Sakura T, Hagihara M, Tomikawa T, Yokoyama Y, Asou N, Ohtake S, Matsumura I, Miyazaki Y, Naoe T, Kiyoi H (2020) Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11. Blood Adv 4(1):66–75. https://doi.org/10.1182/bloodadvances.2019000709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The study was supported by the Capital Characteristic Clinic Project Foundation (Z181100001718126), the National Nature Science Foundation of China (81870125), the National Key Research and Development Program of China (2017YFA0104500), and the Beijing Municipal Science and Technology Commission (Z181100009618032).

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Author notes

  1. Wenbing Duan and Xiaohong Liu contributed equally to this work.

Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematology Disease, Beijing, China

    Wenbing Duan, Xiaohong Liu, Xiaosu Zhao, Jinsong Jia, Jing Wang, Lizhong Gong, Qian Jiang, Ting Zhao, Yu Wang, Xiaohui Zhang, Lanping Xu, Hongxia Shi, Yingjun Chang, Kaiyan Liu, Xiaojun Huang, Yazhen Qin & Hao Jiang

  2. Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Wenbing Duan, Xiaohong Liu, Xiaosu Zhao, Jinsong Jia, Jing Wang, Lizhong Gong, Qian Jiang, Ting Zhao, Yu Wang, Xiaohui Zhang, Lanping Xu, Hongxia Shi, Yingjun Chang, Kaiyan Liu, Xiaojun Huang, Yazhen Qin & Hao Jiang

  3. Peking University Institute of Hematology, Xizhimen South Street No. 11, Peking University People’s Hospital, Beijing, 100044, China

    Yazhen Qin & Hao Jiang

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  1. Wenbing Duan
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Contributions

Hao Jiang and Yazhen Qin designed the study. Wenbing Duan and Xiaohong Liu performed data collection, analysis, and drafted the manuscript. Xiaosu Zhao and Yazhen Qin did the molecular biology examination. Hao Jiang, Yazhen Qin, and Xiaojun Huang provided significant input on the manuscript and data analysis. HongXia Shi did the morphology test. Yingjun Chang did flow cytometry. Jinsong Jia, Jing Wang , Lizhong Gong, Qian Jiang, Ting Zhao, Yu Wang, Xiaohui Zhang, and Lanping Xu, Kaiyan Liu helped to collect data and draft the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yazhen Qin or Hao Jiang.

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This study was approved by the Ethics Committee of Peking University People’s Hospital and was conducted according to the principles of the Helsinki Declaration. All patients signed the informed consent document.

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Duan, W., Liu, X., Zhao, X. et al. Both the subtypes of KIT mutation and minimal residual disease are associated with prognosis in core binding factor acute myeloid leukemia: a retrospective clinical cohort study in single center. Ann Hematol 100, 1203–1212 (2021). https://doi.org/10.1007/s00277-021-04432-z

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