Core Binding Factor Acute Myeloid Leukemia: Advances in the Heterogeneity of , , and Mutations (Review)

Overview

Journal Mol Clin Oncol

Specialty Oncology

Date 2020 Jul 28

PMID 32714530

Citations 7

Authors

Xi Quan

Jianchuan Deng

Affiliations

Soon will be listed here.

Abstract

Core binding factor (CBF) is a heterodimer protein complex involved in the transcriptional regulation of normal hematopoietic process. In addition, CBF molecular aberrations represent approximately 20% of all adult Acute Myeloid Leukemia (AML) patients. Treated with standard therapy, adult CBF AML has higher complete remission (CR) rate, longer CR duration, and better prognosis than that of AML patients with normal karyotype or other chromosomal aberrations. Although the prognosis of CBF AML is better than other subtypes of adult AML, it is still a group of heterogeneous diseases, and the prognosis is often different. Recurrence and relapse-related death are the main challenges to be faced following treatment. Mounting research shows the gene heterogeneity of CBF AML. Therefore, to achieve an improved clinical outcome, the differences in clinical and genotypic characteristics should be taken into account in the evaluation and management of such patients, so as to further improve the risk stratification of prognosis and develop targeted therapy. The present article is a comprehensive review of the differences in some common mutant genes between two subtypes of CBF AML.

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References

Rau R . Beyond KIT in CBF-AML: chromatin and cohesin. Blood. 2016; 127(20):2370-1. PMC: 9278272. DOI: 10.1182/blood-2016-03-707083. View

Kelly L, Gilliland D . Genetics of myeloid leukemias. Annu Rev Genomics Hum Genet. 2002; 3:179-98. DOI: 10.1146/annurev.genom.3.032802.115046. View

Rosnet O, Buhring H, Marchetto S, Rappold I, Lavagna C, Sainty D . Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. Leukemia. 1996; 10(2):238-48. View

Duployez N, Marceau-Renaut A, Boissel N, Petit A, Bucci M, Geffroy S . Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood. 2016; 127(20):2451-9. PMC: 5457131. DOI: 10.1182/blood-2015-12-688705. View

Boissel N, Leroy H, Brethon B, Philippe N, De Botton S, Auvrignon A . Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia. 2006; 20(6):965-70. DOI: 10.1038/sj.leu.2404188. View

Huang G, Shigesada K, Ito K, Wee H, Yokomizo T, Ito Y . Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. EMBO J. 2001; 20(4):723-33. PMC: 145428. DOI: 10.1093/emboj/20.4.723. View

Mead A, Linch D, Hills R, Wheatley K, Burnett A, Gale R . FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood. 2007; 110(4):1262-70. DOI: 10.1182/blood-2006-04-015826. View

Cammenga J, Horn S, Bergholz U, Sommer G, Besmer P, Fiedler W . Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate. Blood. 2005; 106(12):3958-61. DOI: 10.1182/blood-2005-02-0583. View

Solh M, Yohe S, Weisdorf D, Ustun C . Core-binding factor acute myeloid leukemia: Heterogeneity, monitoring, and therapy. Am J Hematol. 2014; 89(12):1121-31. DOI: 10.1002/ajh.23821. View

10.

Speck N, Gilliland D . Core-binding factors in haematopoiesis and leukaemia. Nat Rev Cancer. 2002; 2(7):502-13. DOI: 10.1038/nrc840. View

11.

Cairoli R, Beghini A, Morello E, Grillo G, Montillo M, Larizza L . Imatinib mesylate in the treatment of Core Binding Factor leukemias with KIT mutations. A report of three cases. Leuk Res. 2005; 29(4):397-400. DOI: 10.1016/j.leukres.2004.10.005. View

12.

Paschka P, Dohner K . Core-binding factor acute myeloid leukemia: can we improve on HiDAC consolidation?. Hematology Am Soc Hematol Educ Program. 2013; 2013:209-19. DOI: 10.1182/asheducation-2013.1.209. View

13.

Chen X, Dou H, Wang X, Huang Y, Lu L, Bin J . KIT mutations correlate with adverse survival in children with core-binding factor acute myeloid leukemia. Leuk Lymphoma. 2017; 59(4):829-836. DOI: 10.1080/10428194.2017.1361025. View

14.

Marcucci G, Mrozek K, Ruppert A, Maharry K, Kolitz J, Moore J . Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study. J Clin Oncol. 2005; 23(24):5705-17. DOI: 10.1200/JCO.2005.15.610. View

15.

Jawhar M, Dohner K, Kreil S, Schwaab J, Shoumariyeh K, Meggendorfer M . KIT D816 mutated/CBF-negative acute myeloid leukemia: a poor-risk subtype associated with systemic mastocytosis. Leukemia. 2019; 33(5):1124-1134. PMC: 6756067. DOI: 10.1038/s41375-018-0346-z. View

16.

Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R . Normal and oncogenic forms of the receptor tyrosine kinase kit. Stem Cells. 2004; 23(1):16-43. DOI: 10.1634/stemcells.2004-0117. View

17.

Thiel V, Giaimo B, Schwarz P, Soller K, Vas V, Bartkuhn M . Heterodimerization of AML1/ETO with CBFβ is required for leukemogenesis but not for myeloproliferation. Leukemia. 2017; 31(11):2491-2502. PMC: 5668496. DOI: 10.1038/leu.2017.105. View

18.

Kottaridis P, Gale R, Frew M, Harrison G, Langabeer S, BELTON A . The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the.... Blood. 2001; 98(6):1752-9. DOI: 10.1182/blood.v98.6.1752. View

19.

Schessl C, Rawat V, Cusan M, Deshpande A, Kohl T, Rosten P . The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J Clin Invest. 2005; 115(8):2159-68. PMC: 1174917. DOI: 10.1172/JCI24225. View

20.

Pollyea D . New drugs for acute myeloid leukemia inspired by genomics and when to use them. Hematology Am Soc Hematol Educ Program. 2018; 2018(1):45-50. PMC: 6245963. DOI: 10.1182/asheducation-2018.1.45. View