Presence of leukemic clone‐specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B‐cell precursor acute lymphoblastic leukemia

Author:

Kacanski Natasa1,Kolarovic Jovanka12,Kostic Tatjana3,Marjanovic Irena3,Janic Dragana4,Pavlovic Sonja3,Karan‐Djurasevic Teodora3ORCID

Affiliation:

1. Institute for Child and Youth Health Care of Vojvodina Novi Sad Serbia

2. Faculty of Medicine University of Novi Sad Novi Sad Serbia

3. Institute of Molecular Genetics and Genetic Engineering University of Belgrade Belgrade Serbia

4. Institute for Oncology and Radiology of Serbia Belgrade Serbia

Abstract

AbstractIntroductionChildhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) can be traced back to birth using leukemic clone‐specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease.MethodsWe retrospectively analyzed neonatal blood spots (Guthrie cards) of 24 patients with childhood BCP‐ALL aged 1–9.6 years (median 3.1 years) for the presence of clonotypic IGH rearrangements identified in diagnostic bone marrow samples. Based on the sequences of IGH rearrangements, 2 patient‐specific primers were designed for each patient and used in semi‐nested polymerase chain reaction for the detection of preleukemic clones at birth.ResultsClonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients (13/24). In two cases with double IGH rearrangements detected at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card‐positive findings were significantly more frequent in children ≤5 years of age than in older children (p = 0.011). Regarding patients' characteristics at birth and at diagnosis, Guthrie card‐positivity was not associated with sex, birth weight and mother's age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis.ConclusionOur study confirms that a large proportion of childhood BCP‐ALL originates in utero, regardless of the molecular subtype defined by chromosomal aberrations. The observed trend toward younger age at diagnosis in Guthrie card‐positive versus Guthrie card‐negative patients implies that the age at diagnosis depends on the presence of preleukemic clone at birth, as well as on the timing of postnatal transforming genetic events.

Funder

Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja

Publisher

Wiley

Subject

Biochemistry (medical),Clinical Biochemistry,Hematology,General Medicine

Reference40 articles.

1. Advances in the diagnosis and treatment of pediatric acute lymphoblastic leukemia;Inaba H;J Clin Med,2021

2. Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases;Li JF;Proc Natl Acad Sci U S A,2018

3. A causal mechanism for childhood acute lymphoblastic leukaemia;Greaves M;Nat Rev Cancer,2018

4. Genome‐wide analysis of genetic alterations in acute lymphoblastic leukaemia;Mullighan CG;Nature,2007

5. Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse‐associated genes;Lindqvist CM;Oncotarget,2016

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3