CBL (casitas-B-lineage lymphoma) gene mutations have been identified in approximately 15% of chronic myelomonocytic leukemia, 15% of juvenile myelomonocytic leukemia, 15% of secondary AML(from MDS or MDS/MPN overlap syndrome) and rare or absent in polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic eosinophilic leukemia and MDS. Also, CBL mutations are found in only 1% of de novo acute leukemias and tend to be associated with core binding factor acute myeloid leukemia (AML) among AML cases. CBL is a Ras pathway gene and has been associated with hereditary myeloid disorders. CBL ubiquitinylates and degrades activated receptor and non-receptor tyrosine kinases via the E3-ligase activity of its RING domain. CBL also acts as an adaptor for downstream cell signal transduction, via its tyrosine kinase binding domain. Most variants of the CBL protein are missense substitutions in the zinc binding RING domain (amino acids 366-420) (exons 8-9) that abrogate CBL ubiquitin ligase activity but retain other functions. Pathogenic mutations are believed to be oncogenic by a variety of potential mechanisms including increased Ras pathway activation, aberrant phosphoSTAT5 and/or increased KIT expression in different cellular contexts. Occasionally, two CBL mutations may be present or CBL mutations may be associated with uniparental disomy. In addition, CBL mutations may occur together with mutations in other genes ( RUNX1, ASXL1, TET2 or EZH2 ). According to some studies, mutations of CBL may be associated with reduced overall survival in MDS.

This gene is a known cancer gene.

This gene is a known cancer gene.