Correlation of the surface expression of thymic stromal lymphopoietin receptor with the presence of CRLF2 gene rearrangements in children with B-lineage acute lymphoblastic leukemia

Int J Lab Hematol. 2023 Jun;45(3):337-343. doi: 10.1111/ijlh.14028. Epub 2023 Feb 7.

Abstract

Introduction: In this study, we aimed to compare the immunophenotype of tumor cells in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harboring rearrangements of the CRLF2 gene with that in children without such aberrations with a specific focus on the surface expression of the related protein thymic stromal lymphopoietin receptor (TSLPR).

Methods: We examined bone marrow samples from 46 patients with primary BCP-ALL who had CRLF2 rearrangements detected by FISH (CRLF2(+) cohort). A total of 140 consecutive patients with intact CRLF2 were included in a control CRLF2(-) cohort. TSLPR expression was studied by flow cytometry.

Results: The majority of CRLF2(+) patients were conventionally positive (≥20% positive cells) for TSLPR (33 of 46, 71.7%). Among the remaining children in this group, two were completely TSLPR-negative, seven had less than 10% TSLPR-positive cells, and four had between 10% and 20% TSLPR-positive cells. By contrast, the majority of CRLF2(-) patients had no TSLPR-positive cells (119 of 140, 85.0%), while in 15 cases (10.7%), the percentage of TSLPR-positive cells was below 10%, and in six cases (4.3%), it was between 10% and 20%. Receiver operator characteristic analysis revealed a threshold of only 1.6% TSLPR-positive cells for the effective prediction of the presence of CRLF2 rearrangement. Moreover, this threshold retained its predictive value when only children with low TSLPR positivity were studied.

Conclusion: When surface TSLPR is detected at the diagnosis of BCP-ALL, close attention should be given to the search for chromosomal aberrations involving CRLF2 at any level of expression.

Keywords: CRLF2; acute lymphoblastic leukemia; flow cytometry.

MeSH terms

  • Chromosome Aberrations
  • Gene Rearrangement
  • Humans
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Receptors, Cytokine / genetics
  • Thymic Stromal Lymphopoietin

Substances

  • Thymic Stromal Lymphopoietin
  • CRLF2 protein, human
  • Receptors, Cytokine