High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia

Cytokine. 2022 Jul;155:155896. doi: 10.1016/j.cyto.2022.155896. Epub 2022 May 7.

Abstract

The P2RY8-CRLF2 and IGH-CRLF2 rearrangements induce the overexpression of cytokine receptor-like factor 2 (CRLF2) and have been associated with relapse and poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Additionally, they are frequently documented in high-risk Hispanic populations. To better understand the potential causes of the adverse prognosis of childhood B-ALL in Mexico, we analyzed these rearrangements and the CRLF2 mRNA and protein levels in 133 Mexican children with B-ALL. We collected bone marrow samples at diagnosis and evaluated the CRLF2 gene expression by qRT-PCR and the total CRLF2 protein by flow cytometry. P2RY8-CRLF2 and IGH-CRLF2 were detected by RT-PCR and FISH, respectively. The median time of follow-up to determine the prognostic significance of the CRLF2 abnormalities was three years. In 82% of the participants, the mRNA levels correlated with the cell-surface and intracellular CRLF2 protein levels. The P2RY8-CRLF2 rearrangement was present in 31.5% (42/133) of the patients, while the IGH-CRLF2 rearrangement was detected in 13.5% (9/67) of patients with high expression of CRLF2 (6.8% of the total sample). CRLF2 copy number variations (gain) were also detected in 7.5% (5/67) of patients with high protein levels. The overall survival (OS) presented significantly lower rates in patients with high white blood cell count (≥50x109/L) regardless of CRLF2 expression, but high levels of CRLF2 gene expression appears to contribute to the reduction of OS within this group of patients. In conclusion, in our cohort, a high occurrence of CRLF2 abnormalities was documented, particularly the P2RY8-CRLF2 rearrangement, which might represent a characteristic of the Mexican population. Targeted therapy to treat this group of patients could improve OS.

Keywords: Acute lymphoblastic leukemia; CRLF2 gene expression; CRLF2 rearrangements; Cell-surface CRLF2; IGH-CRLF2; Intracellular CRLF2; Mexican children; P2RY8-CRLF2; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Copy Number Variations
  • Humans
  • Mexico
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Prognosis
  • RNA, Messenger / genetics
  • Receptors, Cytokine / genetics

Substances

  • CRLF2 protein, human
  • RNA, Messenger
  • Receptors, Cytokine