SRSF2 mutation cooperates with ASXL1 truncated alteration to accelerate leukemogenesis
Pinpin Sui, Guo Ge, Shi Chen, Jiaojiao Bai, Ivan P. Rubalcava, Hui Yang, Ying Guo, Peng Zhang, Ying Li, Edward A. Medina, Mingjiang Xu, Omar Abdel‐Wahab, Robert K. Bradley, Feng‐Chun Yang
Abstract
Additional sex combs-like 1 (ASXL1) gene is highly mutated in a spectrum of myeloid malignancies, including ~49% of chronic myelomonocytic leukemia (CMML) [ 1 ], ~10% of acute myeloid leukemia (AML) [ 2 ], ~21% of myelodysplastic syndromes (MDS) [ 3 ], ~10% of myeloproliferative neoplasms (MPN) [ 4 ], and ~8% of juvenile myelomonocytic leukemia (JMML) [ 5 ]. The majority of ASXL1- mutated patients had other concurrent gene mutations, and splicing factors ( SRSF2 , U2AF1 , ZRZR2 , SF3B1 ) were most frequently mutated in myeloid malignancies [ 6 , 7 ]. Of note, patients with a cooccurring mutation of ASXL1 and splicing factor mutations have a worse prognosis than patients with either mutation alone or without both mutations [ 8 ], suggesting a possible synergistic effect of the two mutations in myeloid malignancy progression.