High CRLF2 Expression Could Identify Acute Lymphoblastic Leukemia Patients with Poor Outcome but Not IKZF1

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.

Keywords

• acute lymphoblastic leukemia
• cytokine receptor-like factor 2
• ikzf 1
• qrt-pcr