China
Africa
Explore chapters and articles related to this topic
Gene Expression Profiling to Detect New Treatment Targets in Leukemia and Lymphoma: A Future Perspective
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Torsten Haferlach, Wolfgang Kern, Alexander Kohlmann
However, regarding the biological heterogeneity of AML in general and of AML with normal karyotype in particular, it is anticipated that further large-scale studies in the context of clinical trials are needed to fully characterize and validate novel and clinically relevant subgroups in AML and by doing so to define new targets for individual treatment. A recent example is the study of Bullinger et al. who further subclassified 93 patients with core binding factor (CBF) leukemias (AML1-ETO and CBFB-MYH11) in different risk groups (23).
Precision medicine in acute myeloid leukemia
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Cytogenetic abnormalities used in the WHO classification (Vardiman et al., 2009) are shown in Table 10.1. Approximately 10% of adult AML and 20% of childhood AML are classified as having core binding factor (CBF) leukemia with balanced chromosomal rearrangements that disrupt gene RUNX1 (also known as CBFA2 or AML1), which plays a critical role in hematopoiesis and leukemogenesis (Lam and Zhang, 2012; Marcucci, 2006; Metzeler and Bloomfield, 2017; Mrózek et al., 2008; Sangle and Perkins, 2011; Utsun and Marcucci, 2015; Yamagata et al., 2005). Patients with two specific, clonal, recurring cytogenetic abnormalities t(8;21)(q22;q22), inv(16)(p13.1q22) or t(16;16)(p13.1q22) are called CBF AML. Compared to other cytogenetic AML subgroups, CBF AML is considered a more favorable subset of AML (Table 10.2). CBF AML results in the formation of hybrid fusion genes called RUNX1-RUNX1T1 (also known as AML1-ETO) and CBFB-MYH11, which can be quantified in patients before, during, and after the therapy, including stem cell transplantation (Yin et al., 2012). Favorable karyotype patients have a good prognosis with complete remission rates exceeding 90%, a five-year survival of at least 65%, and relapse rates too low and salvage rates too high to benefit from routine use of allograft in first complete remission (Smith et al., 2011).
Acute Myeloid Leukemia An Introduction
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
Core-binding factor (CBF) leukemias refer to AML with t(8;21)(q22;q22) and inv(16)(p13q22), characterized by disruption of the RUNX1 gene at 21q22 and CBFB gene at 16q22, respectively. The most common type of AML with rearranged CBF is AML with t(8;21), which leads to fusion of RUNX1 and RUNX1T1 (CBFA2T1; previously known as ETO). Inversion of chromosome 16 or t(16;16) results in the fusion of the CBF beta gene CBFB with MYH11 (gene encoding smooth muscle myosin heavy chain). CBF+ AML with either inv(16)/t(16;16) or t(8;21) constitutes AML subgroups with a favorable prognosis, regardless of additional chromosomal changes or complexity.
AML with inv(16)/t(16;16) and high-risk cytogenetic abnormalities: atypical features and unfavorable outcome
Published in Hematology, 2022
Nada Assaf, Christine Lefebvre, Victoria Raggueneau, Geoffroy Guignedoux, Alice Marceau-Renaut, Simon Chevalier, Sylvie Tondeur, Dominique Bories, Riad Benramdane, Philippe Rousselot, Christine Terré
AML with inv(16) is associated with a good prognosis, characterized by high complete remission rates and long-term overall survival [2]. Favorable outcomes in AML inv(16) are affected by the presence of FLT3-TKD mutations and previous therapy, [2] but not rare fusion transcripts [13]. The clinical behavior of our patients seems to parallel the poor outcome of the additional high-risk cytogenetic abnormalities [10] rather than the favorable prognosis of inv(16). As previously stated, the effect of secondary abnormalities on the prognosis of CBFB-MYH11 positive AML is still debatable. While some studies observed a poor outcome of inv(16) AML with additional monosomy 7/del7q [9], tp53 mutation [17] or complex karyotype [5], others do not report a worse outcome [3,18–20]. These studies, however, considered each secondary abnormality as a single factor in univariate analysis. To date, no published study has compared inv(16) AML with high risk abnormalities to AML with inv(16) as a sole abnormality or other secondary cytogenetic abnormalities. In addition to our case series, 2 published case reports describe a high-risk behavior of this CBF AML subgroup [6,7]. In their refinement of the ELN2017 classification, Herold et al describe a case of AML inv(16) and mutated tp53 treated with HSCT at first intention [17].
Molecular targets for the treatment of AML in the forthcoming 5th World Health Organization Classification of Haematolymphoid Tumours
Published in Expert Review of Hematology, 2022
Matteo Molica, Salvatore Perrone
Among patients with core binding factor (CBF) AML (i.e. those with RUNX1::RUNX1T1 fusion and CBFB::MYH11 fusion), KIT mutations have been observed in up to 25% of cases and may correlate with significantly lower prognosis compared with KIT–wild-type disease when treated with 7 + 3 induction [86]. Imatinib, dasatinib, and midostaurin show activity against c-KIT, among other targets, so repurposing these drugs in CBF AML seems feasible. In a phase II trial including 89 patients with de novo CBF AML, dasatinib was administered with 7 + 3 induction and high-dose cytarabine consolidation and then pursued for 1 year as maintenance [87]. The 4-year cumulative incidence of relapse was 33% with an event-free survival of 58%; these results appeared superior compared with historical outcomes observed after chemotherapy alone. Interestingly, in patients with CBF AML treated with FLAG in combination with either idarubicin and/or gemtuzumab ozogamicin, the presence of KIT mutations did not correlate with an inferior outcome, indicating that more intensive treatments could favorably impact on the negative prognostic effects of KIT mutations [88].
The research progress of circular RNAs in hematological malignancies
Published in Hematology, 2019
Tingting Ji, Qiuni Chen, Shandong Tao, Yuye Shi, Yue Chen, Li Shen, Chunling Wang, Liang Yu
Circ-CBFB, an oncogene in CLL, was generated by the CBFB gene. Xia et al. [15] found that the circ-CBFB expression was obviously higher in CLL groups than control groups, which corresponded to a significantly short survival time, indicating that circ-CBFB was of great value in the CLL diagnosis and prognosis. Functionally, circ-CBFB facilitated CLL cells reproduction and inhibited cells death, which could be weakened to block cells in G0/G1 phase by knocking out circ-CBFB. Mechanistically, circ-CBFB could enhance the expression level of FZD3 by adsorbing miR-607. The Wnt/β-catenin pathway was then activated, which had a positive relation with CLL progression [44]. Taken together, the circ-CBFB related signaling pathway played a vital role in CLL cells progression and made it a potential therapeutic target.