Clinical, biological, and outcome features of P2RY8‐CRLF2 and CRLF2 over‐expression in pediatric B‐cell precursor acute lymphoblastic leukemia according to the CCLG‐ALL 2008 and 2018 protocol

Abstract Objectives CRLF2 alterations are associated with B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). This study aimed to explore the clinical, biological, and outcome features of pediatric BCP‐ALL with CRLF2 abnormalities. Methods This study enrolled 630 childhood BCP‐ALLs treated on CCLG‐ALL 2008 or 2018 protocol. P2RY8‐CRLF2 was determined by Sanger sequencing and CRLF2 expression was evaluated by qRT‐PCR. The correlation between clinical, biological features and outcomes with P2RY8‐CRLF2 or CRLF2 over‐expression were analyzed. Results P2RY8‐CRLF2 and CRLF2 over‐expression were found in 3.33% and 5.71% respectively. P2RY8‐CRLF2 was associated with male, higher frequency of CD7 expression, high WBC and MRD before consolidation. CRLF2 over‐expression showed ETV6 ‐ RUNX1 − , higher frequency of CD22, CD34, CD66c, CD86 expression, hyperdiploidy and high MRD at early treatment. The lower overall survival (OS) was found in patients with P2RY8 ‐ CRLF2 and confined only in IR group. Furthermore, adverse event‐free survival and OS of P2RY8‐CRLF2 were discovered comparing to those without known fusions or treated on CCLG‐ALL 2008 protocol. However, P2RY8‐CRLF2 was not confirmed as independent prognostic factors and no prognostic impact of CRLF2 over‐expression was found. Conclusions These findings indicate P2RY8‐CRLF2 identifies a subset of patients with specific features and adverse outcomes that could be improved by risk‐directed treatment.