Heritable GATA2 mutations associated with familial AML-MDS: a case report and review of literature
Identifieur interne : 002A29 ( Main/Exploration ); précédent : 002A28; suivant : 002A30Heritable GATA2 mutations associated with familial AML-MDS: a case report and review of literature
Auteurs : Juehua Gao [États-Unis] ; Ryan D. Gentzler [États-Unis] ; Andrew E. Timms [États-Unis] ; Marshall S. Horwitz [États-Unis] ; Olga Frankfurt [États-Unis] ; Jessica K. Altman [États-Unis] ; Loann C. Peterson [États-Unis]Source :
- Journal of Hematology & Oncology [ 1756-8722 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : GATA2 Transcription Factor.
- genetics : Leukemia, Myeloid, Myelodysplastic Syndromes.
- Acute Disease, Base Sequence, DNA Mutational Analysis, Family Health, Female, Heterozygote, Humans, Karyotyping, Middle Aged, Mutation, Missense.
Abstract
A 50-year-old woman was diagnosed with acute myeloid leukemia (AML). She has history of thrombocytopenia for 25 years and a significant family history of thrombocytopenia, affecting her mother, siblings and their children, as well as her own children. Both her mother and maternal aunt died from myelodysplastic syndrome (MDS). Additional genetic analysis was performed and identified two heterozygous missence mutations in the second zinc finger domain of GATA2 gene (p.Thr358Lys, and p.Leu359Val), occurring in cis on the same allele. Given the patient’s family history and clinical manifestation, this was interpreted as an acute myeloid leukemia with heritable GATA2 mutations associated with familial AML-MDS. Germline GATA2 mutations are involved in a group of complex syndromes with overlapping clinical features of immune deficiency, lymphedema and propensity to acute myeloid leukemia or myelodysplastic syndrome (AML-MDS). Here we reported a case of familial AML-MDS with two novel GATA2 mutations. This case illustrates the importance of recognizing the clinical features for this rare category of AML-MDS and performing the appropriate molecular testing. The diagnosis of heritable gene mutations associated familial AML-MDS has significant clinical implication for the patients and affected families. Clinical trials are available to further investigate the role of allogeneic hematopoietic stem cell transplant in managing these patients.
Url:
DOI: 10.1186/1756-8722-7-36
PubMed: 24754962
PubMed Central: 4006458
Affiliations:
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Huron Street, Chicago, IL 60611, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Northwestern University Feinberg School of Medicine, 251 E. Huron Street, Chicago, IL 60611</wicri:regionArea><wicri:noRegion>IL 60611</wicri:noRegion></affiliation></author><author><name sortKey="Gentzler, Ryan D" sort="Gentzler, Ryan D" uniqKey="Gentzler R" first="Ryan D" last="Gentzler">Ryan D. Gentzler</name><affiliation wicri:level="1"><nlm:aff id="I2">Department of Internal Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, 251 E. Huron Street, Chicago, IL 60611, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, 251 E. 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Huron Street, Chicago, IL 60611, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, 251 E. Huron Street, Chicago, IL 60611</wicri:regionArea><wicri:noRegion>IL 60611</wicri:noRegion></affiliation></author><author><name sortKey="Altman, Jessica K" sort="Altman, Jessica K" uniqKey="Altman J" first="Jessica K" last="Altman">Jessica K. Altman</name><affiliation wicri:level="1"><nlm:aff id="I2">Department of Internal Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, 251 E. Huron Street, Chicago, IL 60611, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, 251 E. Huron Street, Chicago, IL 60611</wicri:regionArea><wicri:noRegion>IL 60611</wicri:noRegion></affiliation></author><author><name sortKey="Peterson, Loann C" sort="Peterson, Loann C" uniqKey="Peterson L" first="Loann C" last="Peterson">Loann C. Peterson</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Pathology, Northwestern University Feinberg School of Medicine, 251 E. Huron Street, Chicago, IL 60611, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Northwestern University Feinberg School of Medicine, 251 E. Huron Street, Chicago, IL 60611</wicri:regionArea><wicri:noRegion>IL 60611</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of Hematology & Oncology</title><idno type="eISSN">1756-8722</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acute Disease</term><term>Base Sequence</term><term>DNA Mutational Analysis</term><term>Family Health</term><term>Female</term><term>GATA2 Transcription Factor (genetics)</term><term>Heterozygote</term><term>Humans</term><term>Karyotyping</term><term>Leukemia, Myeloid (genetics)</term><term>Middle Aged</term><term>Mutation, Missense</term><term>Myelodysplastic Syndromes (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Analyse de mutations d'ADN</term><term>Caryotypage</term><term>Facteur de transcription GATA-2 (génétique)</term><term>Femelle</term><term>Humains</term><term>Hétérozygote</term><term>Leucémie myéloïde (génétique)</term><term>Maladie aigüe</term><term>Mutation faux-sens</term><term>Santé de la famille</term><term>Syndromes myélodysplasiques (génétique)</term><term>Séquence nucléotidique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>GATA2 Transcription Factor</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Leukemia, Myeloid</term><term>Myelodysplastic Syndromes</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur de transcription GATA-2</term><term>Leucémie myéloïde</term><term>Syndromes myélodysplasiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Acute Disease</term><term>Base Sequence</term><term>DNA Mutational Analysis</term><term>Family Health</term><term>Female</term><term>Heterozygote</term><term>Humans</term><term>Karyotyping</term><term>Middle Aged</term><term>Mutation, Missense</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Analyse de mutations d'ADN</term><term>Caryotypage</term><term>Femelle</term><term>Humains</term><term>Hétérozygote</term><term>Maladie aigüe</term><term>Mutation faux-sens</term><term>Santé de la famille</term><term>Séquence nucléotidique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A 50-year-old woman was diagnosed with acute myeloid leukemia (AML). She has history of thrombocytopenia for 25 years and a significant family history of thrombocytopenia, affecting her mother, siblings and their children, as well as her own children. Both her mother and maternal aunt died from myelodysplastic syndrome (MDS). Additional genetic analysis was performed and identified two heterozygous missence mutations in the second zinc finger domain of GATA2 gene (p.Thr358Lys, and p.Leu359Val), occurring in cis on the same allele. Given the patient’s family history and clinical manifestation, this was interpreted as an acute myeloid leukemia with heritable GATA2 mutations associated with familial AML-MDS. Germline GATA2 mutations are involved in a group of complex syndromes with overlapping clinical features of immune deficiency, lymphedema and propensity to acute myeloid leukemia or myelodysplastic syndrome (AML-MDS). Here we reported a case of familial AML-MDS with two novel GATA2 mutations. This case illustrates the importance of recognizing the clinical features for this rare category of AML-MDS and performing the appropriate molecular testing. The diagnosis of heritable gene mutations associated familial AML-MDS has significant clinical implication for the patients and affected families. Clinical trials are available to further investigate the role of allogeneic hematopoietic stem cell transplant in managing these patients.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Murphy, Km" uniqKey="Murphy K">KM Murphy</name></author><author><name sortKey="Levis, M" uniqKey="Levis M">M Levis</name></author><author><name sortKey="Hafez, Mj" uniqKey="Hafez M">MJ Hafez</name></author><author><name sortKey="Geiger, T" uniqKey="Geiger T">T Geiger</name></author><author><name sortKey="Cooper, Lc" uniqKey="Cooper L">LC Cooper</name></author><author><name sortKey="Smith, Bd" uniqKey="Smith B">BD Smith</name></author><author><name sortKey="Small, D" uniqKey="Small D">D Small</name></author><author><name sortKey="Berg, Kd" uniqKey="Berg K">KD Berg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gorello, P" uniqKey="Gorello P">P Gorello</name></author><author><name sortKey="Cazzaniga, G" 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uniqKey="Minelli A">A Minelli</name></author><author><name sortKey="Maserati, E" uniqKey="Maserati E">E Maserati</name></author><author><name sortKey="Giudici, G" uniqKey="Giudici G">G Giudici</name></author><author><name sortKey="Tosi, S" uniqKey="Tosi S">S Tosi</name></author><author><name sortKey="Olivieri, C" uniqKey="Olivieri C">C Olivieri</name></author><author><name sortKey="Bonvini, L" uniqKey="Bonvini L">L Bonvini</name></author><author><name sortKey="De Filippi, P" uniqKey="De Filippi P">P de Filippi</name></author><author><name sortKey="Biondi, A" uniqKey="Biondi A">A Biondi</name></author><author><name sortKey="Lo Curto, F" uniqKey="Lo Curto F">f Lo Curto</name></author><author><name sortKey="Pasquali, F" uniqKey="Pasquali F">F Pasquali</name></author><author><name sortKey="Danesino, C" uniqKey="Danesino C">C Danesino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kwong, Yl" uniqKey="Kwong Y">YL Kwong</name></author><author><name sortKey="Ng, Mh" uniqKey="Ng M">MH Ng</name></author><author><name sortKey="Ma, Sk" uniqKey="Ma S">SK Ma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cuellar Rodriguez, J" uniqKey="Cuellar Rodriguez J">J Cuellar-Rodriguez</name></author><author><name sortKey="Gea Banacloche, J" uniqKey="Gea Banacloche J">J Gea-Banacloche</name></author><author><name sortKey="Freeman, Af" uniqKey="Freeman A">AF Freeman</name></author><author><name sortKey="Hsu, Ap" uniqKey="Hsu A">AP Hsu</name></author><author><name sortKey="Zerbe, Cs" uniqKey="Zerbe C">CS Zerbe</name></author><author><name sortKey="Calvo, Kr" uniqKey="Calvo K">KR Calvo</name></author><author><name sortKey="Wilder, J" uniqKey="Wilder J">J Wilder</name></author><author><name sortKey="Kurlander, R" uniqKey="Kurlander R">R Kurlander</name></author><author><name sortKey="Olivier, Kn" uniqKey="Olivier K">KN Olivier</name></author><author><name sortKey="Holland, Sm" uniqKey="Holland S">SM Holland</name></author><author><name sortKey="Hickstein, Dd" uniqKey="Hickstein D">DD Hickstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goldin, Lr" uniqKey="Goldin L">LR Goldin</name></author><author><name sortKey="Kristinsson, Sy" uniqKey="Kristinsson S">SY Kristinsson</name></author><author><name sortKey="Liang, Xs" uniqKey="Liang X">XS Liang</name></author><author><name sortKey="Derolf, Ar" uniqKey="Derolf A">AR Derolf</name></author><author><name sortKey="Landgren, O" uniqKey="Landgren O">O Landgren</name></author><author><name sortKey="Bjorkholm, M" uniqKey="Bjorkholm M">M Bjorkholm</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Washington (État)</li></region><settlement><li>Seattle</li></settlement><orgName><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="Gao, Juehua" sort="Gao, Juehua" uniqKey="Gao J" first="Juehua" last="Gao">Juehua Gao</name></noRegion><name sortKey="Altman, Jessica K" sort="Altman, Jessica K" uniqKey="Altman J" first="Jessica K" last="Altman">Jessica K. Altman</name><name sortKey="Frankfurt, Olga" sort="Frankfurt, Olga" uniqKey="Frankfurt O" first="Olga" last="Frankfurt">Olga Frankfurt</name><name sortKey="Gentzler, Ryan D" sort="Gentzler, Ryan D" uniqKey="Gentzler R" first="Ryan D" last="Gentzler">Ryan D. Gentzler</name><name sortKey="Horwitz, Marshall S" sort="Horwitz, Marshall S" uniqKey="Horwitz M" first="Marshall S" last="Horwitz">Marshall S. Horwitz</name><name sortKey="Peterson, Loann C" sort="Peterson, Loann C" uniqKey="Peterson L" first="Loann C" last="Peterson">Loann C. Peterson</name><name sortKey="Timms, Andrew E" sort="Timms, Andrew E" uniqKey="Timms A" first="Andrew E" last="Timms">Andrew E. Timms</name><name sortKey="Timms, Andrew E" sort="Timms, Andrew E" uniqKey="Timms A" first="Andrew E" last="Timms">Andrew E. Timms</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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