Molecular basis of myelodysplastic/myeloproliferative neoplasms

Abstract

Although the molecular characterization of these myeloid neoplasms is cumbersome in clinical settings, at least at present, the information provided by these studies is of crucial importance for defining their pathophysiology, and may ultimately lead to a molecular classification and a better prognostic definition of myelodysplastic/myeloproliferative neoplasms.

The mutational landscape of 18 investigated genes clearly separates four subtypes of myelodysplastic/myeloproliferative neoplasms

“…Overall, these mutation frequencies are in line with published data, except for a slightly higher frequency of CBL mutations in CMML and the absence of NRAS mutations in MDS/MPN, U. [2][3][4][5]10,[12][13][14] In previous studies the frequency of the CBL mutation was found to be ~10% in CMML instead of the 24% in our study and RAS mutations were detected in 14% of MDS/MPN, U, contrasting with the 0% in the present study.…”

World Health Organization Classification, Evaluation, and Genetics of the Myeloproliferative Neoplasm Variants

“…Cytogenetics: clonal cytogenetic abnormalities in up to 80%; trisomy 8 and del(20q) are the most common, but abnormalities of chromosomes 13,14,17,19, and 12 are also commonly reported. 40 Molecular genetics: mutated NRAS, KRAS, or TET2 in nearly 30% 37 ; mutations of CBL, RUNX1, CEBPA, EZH2, or WT1 in 1%-10% 31,42,55 ; and JAK2 V617F occurs rarely if at all. 40 …”

Specific molecular mutation patterns delineate chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and chronic myelomonocytic leukemia

“…13 In contrast, CSF3R was often mutated in CNL patients (43%, 6 of 14), but rarely in aCML and CMML cases, with only 2 patients each harboring a CSF3R mutation (3%, 2 of 58; 1%, 2 of 146). However, these 4 cases with CSF3R mutation in aCML and CMML showed neutrophil counts below 80% and increased monocyte numbers above 1000/mL in CMML cases and more than 10% neutrophilic precursors in aCML.…”