Distinctive expression of myelomonocytic markers and down‐regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation

Abstract

FLT3-ITD may increase potential for cell proliferation to produce a leukaemic population; NPM1-Mt may cause cells to develop along the myelomonocytic lineage. Extensive analyses and detailed experiments will be required to clarify how NPM1 and FLT3 mutations interact in leukaemogenesis.

FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics

“…Meanwhile, a statistically higher frequency of NPM1 mutation was identified in subjects with AML M5 and lower frequency in AML M2, which was consistent with findings from previous studies (Fröh-ling et al, 2002;Schnittger et al, 2005;Suzuki et al, 2005;Verhaak et al, 2005;Thiede et al, 2006;Huang et al, 2008). Mori et al (2007) provided the evidence that the expression of CD11b and CD14 antigens was significantly associated with NPM1 mutation, suggesting a close association between NPM1 mutation and monocytic features of AML. More frequent NPM1 mutation in AML M5 and a higher frequency of monocytic marker expression in NPM1-mutated subjects indicated a participation of NPM1 mutations in inducing leukemic development towards monocytic features.…”

HLA‐DRneg patients without acute promyelocytic leukemia show distinct immunophenotypic, genetic, molecular, and cytomorphologic characteristics compared to acute promyelocytic leukemia

“…Among those, a clear differential pattern could be reported regarding NPM1 mutations, showing the highest number of patients with NPM1 mutations in our DR À AML. In contrast, NPM1 mutations were completely absent in APL confirming earlier reports (22,(24)(25)(26). Thus, NPM1 mutations have been described to be associated with CD34 negativity (22,24,26) which we could clearly confirm for DR þ AML patients.…”

“…In contrast, NPM1 mutations were completely absent in APL confirming earlier reports (22,(24)(25)(26). Thus, NPM1 mutations have been described to be associated with CD34 negativity (22,24,26) which we could clearly confirm for DR þ AML patients. However, an unexpected finding was that 40% of our CD34 pos DR À AML patients also showed NPM1 mutations.…”

“…It has been described that HLA-DR negativity was not found in patients with low-risk cytogenetics, i.e., CBF-leukemias (9,16). FLT3-ITD mutations have been found in APL and in other predominantly CD34 neg leukemias (18)(19)(20)(21)(22)(23). Leukemia cells of patients with mutations in the NPM1 gene are also reported to be CD34 neg , whereas in APL this gene is not mutated (22,(24)(25)(26)(27).…”

“…FLT3-ITD mutations have been found in APL and in other predominantly CD34 neg leukemias (18)(19)(20)(21)(22)(23). Leukemia cells of patients with mutations in the NPM1 gene are also reported to be CD34 neg , whereas in APL this gene is not mutated (22,(24)(25)(26)(27). More recently, two small studies reported that HLA-DR negativity in non-APL patients was associated with the presence of FLT3 and NPM1 mutations as well as negativity for CD34 (23,27).…”