CMML: Clinical and molecular aspects

Itzykson, Raphaël; Duchmann, Matthieu; Lucas, Nolwenn; Solary, Éric

doi:10.1007/s12185-017-2243-z

Cited by 41 publications

(36 citation statements)

References 73 publications

(90 reference statements)

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“…aging HSCs providing the first-step acquisition of clonal expansion and a bias toward the myeloid lineage (Moran-Crusio et al, 2011;Quivoron et al, 2011), but they are not sufficient to induce myeloid transformation and IL-3Rb hypersensitivity (Itzykson et al, 2017). Our findings suggest that these ABCA1 mutants, due to their loss of myelosuppressive functions, could play a pivotal role in providing a second hit, which cooperates with CH alleles to drive myeloid transformation.…”

Section: Discussionmentioning

confidence: 68%

ABCA1 Exerts Tumor-Suppressor Function in Myeloproliferative Neoplasms

et al. 2020

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Section: Discussionmentioning

confidence: 68%

ABCA1 Exerts Tumor-Suppressor Function in Myeloproliferative Neoplasms

et al. 2020

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“…Chronic myelomonocytic leukemia is classified as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). 30 The molecular mechanisms underlying the onset of CMMoL remain to be fully understood. We show here that GATA2 hypomorphism is one of the pathogenic factors of CMMoL development.…”

Section: Discussionmentioning

confidence: 99%

GATA2 hypomorphism induces chronic myelomonocytic leukemia in mice

et al. 2019

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The transcription factor GATA 2 regulates normal hematopoiesis, particularly in‐ stem cell maintenance and myeloid differentiation. Various heteroallelic GATA 2 gene mutations are associated with a variety of hematological neoplasms, including myelodysplastic syndromes and leukemias. Here, we report that impaired GATA 2 expression induces myelodysplastic and myeloproliferative neoplasm development in elderly animals, and this neoplasm resembles chronic myelomonocytic leukemia in humans. GATA 2 hypomorphic mutant ( G2 f GN / fGN ) mice that were generated by the germline insertion of a neocassette into the Gata2 gene locus avoided the early embryonic lethality observed in Gata2 ‐null mice. However, adult G2 f GN / fGN mice suffered from exacerbated leukocytosis concomitant with progressive anemia and thrombocytopenia and eventually developed massive granulomonocytosis accompanied by trilineage dysplasia. The reconstitution activity of G2 f GN / fGN mouse stem cells was impaired. Furthermore, G2 f GN / fGN progenitors showed myeloid lineage‐biased proliferation and differentiation. Myeloid progenitor accumulation started at a younger age in G2 f GN / fGN mice and appeared to worsen with age. G2 f GN / fGN mice showed increased expression of transcripts encoding cytokine receptors, such as macrophage colony‐stimulating factor receptor and interleukin‐6 receptor, in granulocyte‐monocyte progenitors. This increased expression could be correlated with the hypersensitive granulomonocytic proliferation reaction when the mice were exposed to lipopolysaccharide. Taken together, these observations indicate that GATA 2 hypomorphism leads to a hyperreactive defense response to infections, and this reaction is attributed to a unique intrinsic cell defect in the regulation of myeloid expansion that increases the risk of hematological neoplasm transformation.

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“…Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by persistent monocytosis, macrocytic or normocytic anemia, and thrombocytopenia. 2 We report an unusual case of CMML-associated vasculitis mimicking GCA.…”

Section: Chronic Myelomonocytic Leukemia-related Vasculitis Mimickingmentioning

confidence: 91%