Abstract
Background: Overexpression of cytokine receptor-like factor 2 (CRLF2) caused by different genetic aberrations has been observed in acute lymphoblastic leukemia (ALL) and correlated with poor outcome. Most patients with high CRLF2 expression are clustered in the Philadelphia-like (Ph-like) ALL subgroup. Ph-like ALL is reported to be associated with alterations in IKZF1 gene, encoding the transcription factor Ikaros. Aim: To identify CRLF2 and IKZF1 alterations in Egyptian patients with ALL and to determine their prognostic significance. Methods: Peripheral blood samples from 34 newly diagnosed ALL patients treated at an Egyptian tertiary oncology center and 14 controls were assessed for CRLF2 and IKZF1 mRNA expression using real-time polymerase chain reaction. Results: CRLF2 was significantly overexpressed in ALL patients compared to controls (p = 0.038). The response to treatment was significantly better in patients with low CRLF2 expression (p = 0.029). The rate of remission, relapse and induction death was 82%, 12% and 6% in the low CRLF2 expression group and 41%, 18% and 41% in the high expression one. Overall survival was significantly shorter among ALL with high CRLF2 (p = 0.034). IKZF1 expression level did not differ significantly between patients and controls. Patients with low IKZF1 exhibited significantly higher leucocytic count and lower platelet count (p = 0.038 and 0.044, respectively). IKZF1 overexpression did not correlate significantly with response to treatment or survival. Conclusion: High CRLF2 expression was associated with poor outcome among ALL patients. Further research is needed to improve the diagnostic and therapeutic approaches in ALL patients with poor prognosis.
Highlights
Acute lymphoblastic leukemia (ALL) is a heterogeneous disorder characterized by complex molecular changes such as fusion proteins, copy number alterations, as well as gene mutations 1
In T-cell (T-acute lymphoblastic leukemia (ALL)), many genomic aberrations have been identified, only few were proved to be of prognostic value, and none has been incorporated in therapeutic approaches 3
Our study showed that cytokine receptor-like factor 2 (CRLF2) overexpression was linked to poor treatment outcome and worse survival among ALL patients
Summary
Acute lymphoblastic leukemia (ALL) is a heterogeneous disorder characterized by complex molecular changes such as fusion proteins, copy number alterations, as well as gene mutations 1. Was recognized depending on a gene expression signature of leukemic cells that mimics that of BCRABL1–positive ALL, such leukemic cells do not have a BCR-ABL1 translocation 4. These cases have a highly diverse range of genetic changes that activate tyrosine kinase signaling 5. Overexpression of cytokine receptor-like factor 2 (CRLF2) caused by different genetic aberrations has been observed in acute lymphoblastic leukemia (ALL) and correlated with poor outcome. Aim: To identify CRLF2 and IKZF1 alterations in Egyptian patients with ALL and to determine their prognostic significance. The response to treatment was significantly better in patients with low CRLF2 expression (p = 0.029). Further research is needed to improve the diagnostic and therapeutic approaches in ALL patients with poor prognosis
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