Genetic evolution progression of CMML to AML analyzed by whole-genome sequencing. Homo sapiens

The present study aimed to investigate the genetic changes underlying the progression of CMML transforming to AML. Bone marrow and peripheral blood samples as well as paired oral mucosa cells were collected from two patients who progressed from CMML to AML for whole-genome sequencing to identify recurrent mutations specific to this progression. The architecture of samples (buccal mucosa cells, bone marrow cells and peripheral blood) was constructed to determine the specific mutations. The driver genes and clone with growth advantage were determined using the allele burden of mutations. A total of 693.78 Gb data with average depth of 30X× sequence coverage were obtained. In total, 2,406, 2,908 and 2,976 structural variations (SV) were respectively obtained from buccal mucosa cells, CMML and AML of the patient named MWQ . Additionally, 2,810, 2,614 and 2,190 SV were obtained from buccal mucosa cells, CMML and AML of the patient named SSL , respectively. Several recurrent mutation genes were identified. Variant allele frequencies of mutations were detected and five genes [protein tyrosine phosphatase receptor type S (PTPRS), regulator of nonsense transcripts 2 (UPF2), tripartite motif containing 35 (TRIM35), kinesin family member 18B (KIF18B) and sterile α motif domain containing 4A (SAMD4A)] had higher variant allele frequencies in AML, compared with CMML and buccal mucosa cells. PTPRS, TRIM35, KIF18B, UPF2 and SAMD4A may serve essential roles in the progression from the CMML to AML.