CRLF2 and IKZF1 abnormalities in childhood hematological malignancies other than B-cell Acute Lymphoblastic Leukemia.

IF 2.2 4区 医学 Q3 HEMATOLOGY Leukemia & Lymphoma Pub Date : 2024-12-01 Epub Date: 2024-07-21 DOI:10.1080/10428194.2024.2378817
Dafné Moreno-Lorenzana, Rocío Juárez-Velázquez, Adriana Reyes-León, Daniel Martínez-Anaya, Luis Juárez-Villegas, Martha Zapata Tarrés, Norma López Santiago, Patricia Pérez-Vera
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Abstract

Rearrangements and overexpression of CRLF2 are hallmarks of poor outcomes in BCR::ABL1-like B-ALL, and CRLF2 overexpression is a high-risk marker in T-ALL. However, CRLF2 alterations in pediatric hematologic malignancies other than B-ALL have not been reported. In this study, we analyzed the CRLF2 overexpression, rearrangements (P2RY8::CRLF2 and IGH::CRLF2), activation (pSTAT5 and pERK), and the expression of dominant-negative IKZF1 isoforms (Ik6 and Ik8), implied in CRLF2 dysregulation, in 16 pediatric patients (AML, n = 9; T-ALL, n = 3; LBL, n = 2; HL, n = 1; cytopenia, n = 1). A high frequency of CRLF2 rearrangements and overexpression was found in the 16 patients: 28.6% (4/14) showed CRLF2 overexpression, 93.8% (15/16) were positive for CRLF2 total protein (cell-surface and/or cytoplasmic), while 62.5% (10/16) were positive for P2RY8::CRLF2 and 12.6% (2/16) for IGH::CRLF2. In addition, 43.8% (7/16) expressed Ik6 and Ik8 isoforms. However, only a few patients were positive for the surrogate markers pSTAT5 (14.3%; 2/14) and pERK (21.4%; 3/14).

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儿童血液恶性肿瘤(B 细胞急性淋巴细胞白血病除外)中的 CRLF2 和 IKZF1 异常。
CRLF2的重排和过表达是BCR::ABL1样B-ALL不良预后的标志,而CRLF2的过表达是T-ALL的高危标志。然而,除 B-ALL 外,CRLF2 在小儿血液恶性肿瘤中的改变尚未见报道。在本研究中,我们分析了CRLF2的过表达、重排(P2RY8::CRLF2和IGH::CRLF2)、激活(pSTAT5 和 pERK)以及显性阴性 IKZF1 同工酶(Ik6 和 Ik8)的表达,这意味着 16 名儿科患者(AML,n = 9;T-ALL,n = 3;LBL,n = 2;HL,n = 1;全血细胞减少症,n = 1)中 CRLF2 的失调。在这16名患者中,CRLF2重排和过表达的频率很高:28.6%(4/14)的患者表现为CRLF2过表达,93.8%(15/16)的患者CRLF2总蛋白(细胞表面和/或胞质)阳性,62.5%(10/16)的患者P2RY8::CRLF2阳性,12.6%(2/16)的患者IGH::CRLF2阳性。此外,43.8%(7/16)的患者表达 Ik6 和 Ik8 同工酶。然而,只有少数患者的替代标记物 pSTAT5(14.3%;2/14)和 pERK(21.4%;3/14)呈阳性。
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来源期刊
Leukemia & Lymphoma
Leukemia & Lymphoma 医学-血液学
CiteScore
4.10
自引率
3.80%
发文量
384
审稿时长
1.8 months
期刊介绍: Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor
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