Expression of CRLF2 gene in childhood B lineage lymphoblastic leukemia: A prospective analytical study

Acute lymphoblastic leukemia (ALL) is the most common childhood leukemia with high mortality rate. In 2016 revision of ALL, WHO suggested role of Cytokine Receptor-like Factor 2 (CRLF2) gene overexpression in disease biology. Hence, it is imperative to study the role of CRLF2 gene overexpression with survival outcome.

The present study is a cross sectional prospective analytical study. Children (1-14 years) with B lineage acute lymphoblastic leukemia (B-ALL) were recruited for the study. Children with cardiac disease, endocrine disease, autoimmune disease, any other malignancy, any progressive neurological disease or who have received prior treatment for B-ALL were excluded from the study. CRLF2 overexpression was seen using reverse transcriptase real time PCR while copy number alterations in the pseudoautosomal region (PAR1) genes (CRLF2, CSF2RA, IL3RA) were detected using multiplex ligation-dependent probe amplification (MLPA).

Total 93 children with B-ALL were evaluated for CRLF2 gene expression. The CRLF2 gene expression was found to be overexpressed in 8 (8.6 %) of the children. Eight out of 14 patients with CRLF2 overexpression had duplication of CRLF2 gene with/without accompanying IL3RA, CSF3RA or P2RY8 gene alterations. CRLF2 overexpression was associated with deletions of CSF2RA, IL3RA and/or P2RY8 genes and extra copies of CRLF2 gene. However, CRLF2 gene overexpression was not found to be significantly associated with any of the clinical parameters, response to treatment parameters or survival outcome.

CRLF2 gene is overexpressed in those with IL3RA, CSF2RA and P2RY8 gene deletions. However, CRLF2 overexpression is not associated with survival outcome.