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Mixed Myelodysplastic–Myeloproliferative Neoplasms
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
Numerous molecular abnormalities have been identified in patients with CMML. These include RAS mutation (10%–26%), JAK2 mutations (8%–10%), as well as CBL gene mutation, and RUNX1, ASXL1, NPM1, TET2, and IDH1 or IDH2 mutations [2].
Novel approaches to diagnosis and treatment of Juvenile Myelomonocytic Leukemia
Published in Expert Review of Hematology, 2018
Franco Locatelli, Mattia Algeri, Pietro Merli, Luisa Strocchio
Germ line mutations in CBL, found in as much as 15% of all cases, have been described in children showing several congenital abnormalities that overlap those observed in NF1, NS, and Legius syndrome [9,41,49]. In these patients, JMML appears as the result of loss of heterozygosity (LOH) for the CBL locus in hematopoietic stem/progenitor cells. CBL encodes a member of a family of RING finger proteins, which functions as an E3 ubiquitin ligase and negatively regulates signaling by tyrosine kinases [50]. Using single-nucleotide polymorphism arrays, a region of 11q isodisomy containing the CBL gene was detected in JMML cells, leading to the identification of CBL mutations in 27 of 159 JMML patients [41]. CBL mutations targeting the Y371 amino acid in the linker region have been more commonly reported in JMML and are rare in other myeloid neoplasms [51]. The observation that CBL mutations and other Ras pathway-associated mutations were mutually exclusive suggested the role of CBL in deregulating the Ras pathway in JMML [49,52].
Sorafenib regulates c-CBL gene-mediated chemoresistance in acute myeloid leukemia cells
Published in Hematology, 2023
Qixin Sun, Bingyi Wu, Fanyi Meng, Qianqian Yao, Zhiwei Huang, Jianhui Xu, Zhigang Zhu
When the c-CBL gene was overexpressed, a notable phenomenon was observed in these two kinds of cells: the proportion of cells in the G2/M phase significantly decreased. For HL60 cells, the percent decreased from 13.34 ± 2.38% to 1.93 ± 1.59% (Figure 5(a)), and for THP1 cells, it decreased from 11.89 ± 4.94% to 1.08 ± 2.19% (Figure 5(b)). This result confirms the previous findings that overexpression of the c-CBL gene can significantly inhibit cell proliferation. In addition, a slight increase in the G1 phase in the HL60 or THP1 cell treatment group was observed regardless of the c-CBL gene expression status, which may be related to the experimental reagents, but these changes were not statistically significant.