CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience

Am J Clin Pathol. 2017 Apr 1;147(4):357-363. doi: 10.1093/ajcp/aqx005.

Abstract

Objectives: Cytokine receptor-like factor 2 ( CRLF2 ) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2 + cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL.

Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients.

Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%). Of CRLF2+ cases, 21 (100%) of 21 cases showed CRLF2 rearrangement by fluorescence in situ hybridization, preferentially involving IGH@CRLF2 (15/15). The entire coding region of JAK2 was sequenced in 14 patients with CRLF2+ B-ALL, and nine (64%) were positive for JAK2 mutations.

Conclusions: MFC allows a rapid, inexpensive, and reliable detection of B-ALL with CRLF2 rearrangement that would further facilitate testing for JAK2 mutations for targetable therapy.

Keywords: B-lymphoblastic leukemia/lymphoma; BCR-ABL1–like; CRLF2; FISH; Flow cytometry; JAK2 mutation; Ph-like B-ALL.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Gene Rearrangement*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Janus Kinase 2 / genetics*
  • Janus Kinase 2 / metabolism
  • Male
  • Middle Aged
  • Mutation
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prospective Studies
  • Receptors, Cytokine / genetics*
  • Receptors, Cytokine / metabolism
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • CRLF2 protein, human
  • Receptors, Cytokine
  • JAK2 protein, human
  • Janus Kinase 2