Surface expression of Cytokine Receptor-Like Factor 2 increases risk of relapse in pediatric acute lymphoblastic leukemia patients harboring IKZF1 deletions
| Autor: | Tomasz Ociepa, Grażyna Sobol-Milejska, Monika Lejman, Jerzy Kowalczyk, Wanda Badowska, Michał Matysiak, Alicja Sonsala, Bernarda Kazanowska, Andrzej Kołtan, Katarzyna Derwich, M. Romiszewska, Lukasz Sedek, Wojciech Młynarski, Grażyna Karolczyk, Maciej Niedzwiecki, Patryk Górniak, Joanna Taha, Tomasz Szczepański, Wojciech Fendler, Katarzyna Muszyńska-Rosłan, Agata Pastorczak, Marta Bielska, Joanna Madzio, Magdalena Twardoch, Karin Nebral, Marcin Braun |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty business.industry medicine.medical_treatment Subgroup analysis medicine.disease Gastroenterology Minimal residual disease 03 medical and health sciences Leukemia 030104 developmental biology 0302 clinical medicine Cytokine Oncology Pediatric Acute Lymphoblastic Leukemia 030220 oncology & carcinogenesis Internal medicine medicine Surface expression Relapse risk business Cytokine receptor |
| Zdroj: | Oncotarget. 9:25971-25982 |
| ISSN: | 1949-2553 |
| Popis: | We prospectively examined whether surface expression of Cytokine Receptor-Like Factor 2 (CRLF2) on leukemic blasts is associated with survival and induction treatment response in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Flow cytometric analysis of bone marrow-derived leukemia cells revealed that 7.51% (29/286) of 386 pediatric BCP-ALL patients were CRLF2-positive (CRLF2pos) at diagnosis. The median minimal residual disease (MRD) was lower in CRLF2pos than CRLF2-negative (CRLF2neg) patients on day 15 (MRD15) after induction therapy [0.01% (0.001-0.42%) vs. 0.45% (0.05-3.50%); p=0.001]. By contrast, the MRD15 was higher in Ikaros family Zinc Finger Protein 1 (IKZF1)-deleted BCP-ALL patients than in BCP-ALL patients without IKZF1 deletions [1.18% (0.06-12.0%) vs 0.33% (0.03-2.6%); p=0.003]. Subgroup analysis showed that MRD15 levels were lower in IKZF1Δ/CRLF2pos patients than in IKZF1Δ/CRLF2neg patients [0.1% (0.02-5.06%) vs. 2.9% (0.25-12%); p=0.005]. Furthermore, MRD15 levels were higher in IKZF1WT/CRLF2neg patients than in IKZF1WT/CRLF2pos patients [0.40% (0.04-2.7%) vs. 0.001% (0.001-0.01%)]. Despite the low MRD15 levels, IKZF1Δ/CRLF2pos patients showed poorer relapse-free survival (RFS) than other patient groups (p=0.003). These findings demonstrate that surface CRLF2 expression is associated with increased risk of relapse in pediatric BCP-ALL patients harboring IKZF1 deletions. |
| Databáze: | OpenAIRE |
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