Invariant phenotype and molecular association of biallelic TET2 mutant myeloid neoplasia.

摘要: Somatic TET2 mutations ( MT ) are frequent in myeloid neoplasia (MN), particularly chronic myelomonocytic leukemia (CMML). includes mostly loss-of-function/hypomorphic hits. Impaired activity skews differentiation of hematopoietic stem cells toward proliferating precursors. This study was prompted by the observation biallelic gene inactivations biTET2 i CMML. We speculated that might be associated with distinct clinicohematological features. analyzed 1045 patients MN. Of 82 cases, 66 were , 13 hemizygous and 3 homozygous (uniparental disomy); remaining (denoted − hereafter) either monoallelic (n = 96) or wild-type 823). Truncation found 83% vs 65% cases P .02). hits founder lesions 72% 38% significantly concurrent included SRSF2 (33%; KRAS / NRAS (16%; .03) as compared . When first hit ancestral most common subsequent affected a second followed ASXL1 RAS DNMT3A BiTET2 without any monocytosis showed an absence S RSF2 older had monocytosis, CMML, normal karyotypes, lower-risk disease patients. Hence, while occurred frequently, did not portend faster progression but rather determined monocytic differentiation, consistent its prevalence Additionally, lower odds cytopenias marrow blasts (≥5%) higher dysplasia hypercellularity. Thus, represent auxiliary assessment tool