Erbilgin Yücel, Firtina Sinem, Kirat Elif, Khodzhaev Khusan, Karakas Zeynep, Ünüvar Ayşegül, Ocak Süheyla, Celkan Tülin Tiraje, Zengin Emine, Aylan Gelen Sema, Yildirmak Zeynep Yildiz, Toluk Ozlem, Hatirnaz Ng Ozden, Ozbek Ugur, Sayitoglu Müge
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Topkapı mh, Gureba Hastanesi Cd. No:69, 34093, Fatih, Istanbul, Turkey.
Department of Internal Medicine, Department of Medical Genetics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Biochem Genet. 2025 Jan 9. doi: 10.1007/s10528-024-11018-7.
IKZF1 deletions (ΔIKZF1) are common in precursor B-cell acute lymphoblastic leukemia (B-ALL) and are assumed to have a prognostic impact. We aimed to determine the prognostic implications of ΔIKZF1 and CRLF2 overexpression in pediatric B-ALL. Furthermore, we sought to compare the multiplex polymerase chain reaction (PCR) assay with standard multiplex ligand-dependent probe amplification (MLPA) methods to ascertain IKZF1 status in a clinical context. Seventy-nine diagnoses and 43 relapse B-ALL samples were evaluated for deletions of IKZF1 Δ2-7, Δ4-7, and Δ4-8 by conventional PCR and then sequenced by targeted sequencing. Subsequently, MLPA analysis was performed for ΔIKZF1 detection, and CRLF2 expression was evaluated in 42 diagnose time B-ALL patients by QRT-PCR. ΔIKZF1 was detected in 10 out of 79 diagnose samples (12.66%) and eight of the 43 first relapsed materials (18.60%). Our results revealed no association between survival outcomes with ΔIKZF1 or CRLF2 overexpression status in pediatric B-ALL patients. However, we found ΔIKZF1 was more frequent among relapsed samples, and the deletions showed consistency between diagnose-first/second relapse pairs of samples. These results suggest that ΔIKZF1 may contribute to the development of treatment failure in B-ALL. Furthermore, we demonstrated methodological adjustments in conventional PCR and MLPA for selected alterations in ΔIKZF1.
IKZF1缺失（ΔIKZF1）在前体B细胞急性淋巴细胞白血病（B-ALL）中很常见，并被认为具有预后影响。我们旨在确定ΔIKZF1和CRLF2过表达在儿童B-ALL中的预后意义。此外，我们试图将多重聚合酶链反应（PCR）检测方法与标准多重配体依赖性探针扩增（MLPA）方法进行比较，以在临床环境中确定IKZF1状态。通过常规PCR评估79例初诊和43例复发B-ALL样本中IKZF1 Δ2-7、Δ4-7和Δ4-8的缺失情况，然后通过靶向测序进行测序。随后，进行MLPA分析以检测ΔIKZF1，并通过QRT-PCR评估42例初诊时的B-ALL患者的CRLF2表达。在79例初诊样本中有10例（12.66%）检测到ΔIKZF1，在43例首次复发样本中有8例（18.60%）检测到。我们的结果显示，儿童B-ALL患者的生存结果与ΔIKZF1或CRLF2过表达状态之间无关联。然而，我们发现ΔIKZF1在复发样本中更常见，并且在初诊/首次复发和首次复发/第二次复发的样本对中缺失情况具有一致性。这些结果表明，ΔIKZF1可能导致B-ALL治疗失败。此外，我们展示了针对ΔIKZF1特定改变在常规PCR和MLPA中的方法调整。
