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ASXL1
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Interpretation 2274
Tier 2
ASXL1
Variants
ASXL1 any missense
ASXL1 any mutation
Primary Sites
Blood
Bone Marrow
Tumor Types
Acute Myeloid Leukemia
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Essential Thrombocythemia
MDS with Ring Sideroblasts
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Monocytosis
Primary Myelofibrosis
Thrombocytopenia, Unspecified
Thrombocytosis
Mast Cell Neoplasm
Interpretation

ASXL1 regulates epigenetic functions including histone and chromatin modifications. ASXL1 mutations have been reported in 40-50% of chronic myelomonocytic leukemia(CMML), 20% of myelodsyplastic syndromes, 20-35% of primary myelofibrosis, 15% of systemic mastocytosis, 30% of patients with secondary acute myeloid leukemia and 5-10% of primary acute myeloid leukemia. ASXL1 mutations have also been described in CHIP and CCUS. In CMML, missense mutations of ASXL1 appear to be less common (less than 10% of cases). Nonsense and frameshift mutations (but apparently not missense mutations) of ASXL1 have been reported to carry an adverse prognostic impact in cases of chronic myelomonocytic leukemia. In addition, ASXL1 mutations have been associated with adverse outcome in myelodysplasia, primary myelofibrosis and systemic mastocytosis. Among cases of AML, ASXL1 mutations appear to be associated with adverse prognosis in some subtypes of AML according to some, but not all, studies. ASXL1 mutations may coexist with mutations of splicing factor components, TET2 and RUNX1; for example, co-existence of U2AF1 and ASXL1 mutations have been described in CMML and primary myelofibrosis; While in AML, ASXL1 mutations have been reported to be exclusive of NPM1 mutations according to some studies.

Citations
  1. Patnaik MM, et al. ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients. Leukemia 2014;28(11):2206-12
  2. Guglielmelli P, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia 2014;28(9):1804-10
  3. Haferlach T, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28(2):241-7
  4. Larsson CA, et al. The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome. Mol Cancer Res 2013;11(8):815-27
  5. Abdel-Wahab O, et al. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood 2013;121(18):3563-72
  6. Gelsi-Boyer V, et al. Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol 2012;5():12
  7. Tefferi A, et al. CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. Leukemia 2014;28(7):1494-500
  8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Myelodysplastic Syndromes (Version 1.2019), Myeloproliferative Neoplasms (Version 2.2018), and Acute Myeloid Leukemia (Version 1.2018).
Last updated: 2018-11-12 20:40:39 UTC
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