Evaluation of hypereosinophilia in a case of FLT3-mutant acute myeloid leukemia treated with gilteritinib.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Cold Spring Harbor Molecular Case Studies Pub Date : 2023-07-11 Print Date: 2023-06-01 DOI:10.1101/mcs.a006279

Leslie N Martinez-Gutierrez, Blake C Burgher, Manuel J Glynias, Daniel Alvarado, Elizabeth A Griffiths, Sean T Glenn, Pamela J Sung

{"title":"Evaluation of hypereosinophilia in a case of FLT3-mutant acute myeloid leukemia treated with gilteritinib.","authors":"Leslie N Martinez-Gutierrez, Blake C Burgher, Manuel J Glynias, Daniel Alvarado, Elizabeth A Griffiths, Sean T Glenn, Pamela J Sung","doi":"10.1101/mcs.a006279","DOIUrl":null,"url":null,"abstract":"Acute myeloid leukemias (AMLs) frequently harbor activating mutations in Fms-like tyrosine kinase 3 (FLT3). The use of FLT3 inhibitors (FLT3i) is the standard of care for treatment of newly diagnosed and relapsed patients with AML. Differentiation responses including clinical differentiation syndrome have been previously reported with FLT3i when used as single agents in relapsed disease. We present a case of hypereosinophilia in a patient on FLT3i therapy with persistent FLT3 polymerase chain reaction (PCR) positivity in peripheral blood. We sorted mature leukocytes by lineage to determine if the eosinophils were leukemia-derived. FLT3 PCR and next-generation sequencing analysis demonstrated monocytic differentiation of the FLT3-ITD leukemic clone with reactive hypereosinophilia that was derived from a preleukemic SF3B1, FLT3 wild-type clone. Our case is the first to definitively demonstrate the emergence of clonal FLT3-ITD monocytes with FLT3i and the first to demonstrate a differentiation response following decitabine, venetoclax, and gilteritinib triplet therapy.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 3","pages":""},"PeriodicalIF":1.8000,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/97/MCS006279Mar.PMC10393187.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cold Spring Harbor Molecular Case Studies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/mcs.a006279","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/1 0:00:00","PubModel":"Print","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Acute myeloid leukemias (AMLs) frequently harbor activating mutations in Fms-like tyrosine kinase 3 (FLT3). The use of FLT3 inhibitors (FLT3i) is the standard of care for treatment of newly diagnosed and relapsed patients with AML. Differentiation responses including clinical differentiation syndrome have been previously reported with FLT3i when used as single agents in relapsed disease. We present a case of hypereosinophilia in a patient on FLT3i therapy with persistent FLT3 polymerase chain reaction (PCR) positivity in peripheral blood. We sorted mature leukocytes by lineage to determine if the eosinophils were leukemia-derived. FLT3 PCR and next-generation sequencing analysis demonstrated monocytic differentiation of the FLT3-ITD leukemic clone with reactive hypereosinophilia that was derived from a preleukemic SF3B1, FLT3 wild-type clone. Our case is the first to definitively demonstrate the emergence of clonal FLT3-ITD monocytes with FLT3i and the first to demonstrate a differentiation response following decitabine, venetoclax, and gilteritinib triplet therapy.

Abstract Image

查看原文本刊更多论文

评估一例接受吉特替尼治疗的FLT3突变急性髓性白血病患者的嗜酸性粒细胞增多症。

急性髓性白血病（AML）经常携带Fms样酪氨酸激酶3（FLT3）的激活突变。使用 FLT3 抑制剂（FLT3i）是治疗新诊断和复发急性髓细胞白血病患者的标准疗法。以前曾有报道称，FLT3i 作为单药用于复发疾病时会出现分化反应，包括临床分化综合征。我们报告了一例接受 FLT3i 治疗、外周血中 FLT3 聚合酶链反应（PCR）持续阳性的嗜酸性粒细胞增多症患者。我们按系对成熟白细胞进行了分类，以确定嗜酸性粒细胞是否来源于白血病。FLT3 PCR和下一代测序分析表明，FLT3-ITD白血病克隆的单核细胞分化与反应性高嗜酸性粒细胞增多均来自白血病前SF3B1、FLT3野生型克隆。我们的病例首次明确证明了 FLT3-ITD 单核细胞克隆与 FLT3i 的关系，并首次证明了地西他滨、venetoclax 和吉特替尼三联疗法后的分化反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.20

自引率

0.00%

发文量

期刊介绍： Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.