An Insight about Cytokine Receptor Like Factor 2 Expression in Philadelphia Like Acute Lymphoblastic Leukemia

Abstract

Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) accounts for 15% to 30% of B-cell acute lymphoblastic leukemia in older children, adolescents, and adults and is associated with high rates of conventional treatment failure and relapse. Current clinical trials are assessing the efficacy of the addition of tyrosine kinase inhibitors (TKIs) to chemotherapy for children and adults with Ph-like ALL harboring ABL class translocations or Cytokine Receptor Like Factor 2(CRLF2) rearrangements and other JAK pathway alterations. In this article we highlight CRLF2possible role in Diagnosis of Philadelphia Like Acute Lymphoblastic Leukemia.Ph-like ALL is characterized by a wide range of genetic alterations that dysregulate several cytokine receptor and kinase signaling pathways, including CRLF2 rearrangement in half of the cases and translocation of non-receptor tyrosine kinases (predominantly ABL-class and Janus kinases).Overexpression of cytokine receptor-like factor 2 (CRLF2) resulting from its genomic rearrangement is the most frequent genetic alteration found in Philadelphia chromosome-like (Ph-like) B-cell acute lymphoblastic leukemia (B-ALL), a high-risk leukemia. Detection of CRLF2 expression by multiparameter flow cytometry has been proposed as a screening tool for the identification of Ph-like B-ALL. However, the prognostic relevance of flow cytometric expression of CRLF2 in pediatric B-ALL is not very clear. Additionally, its association with common copy number alterations (CNA) has not been studied in detail.Conclusion:The mechanisms of CRLF2 overexpression in leukemia are not fully understood but several studies show that it has a prognostic impact. JAK and mTOR inhibitors have been explored in preclinical models as potential therapies targeting CRLF2-rearranged ALL.