title: Characterization of CD34+ hematopoietic progenitor cells in JAK2V617F and CALR-mutated myeloproliferative neoplasms.
abstract: Mutations in JAK2 or CALR are observed in patients with myeloproliferative neoplasms (MPN). To get further insight in the dynamics of the mutant clone, we assessed the mutant allele burden in hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs) and granulocytes from 138 patients [51 polycythemia vera (PV), 58 essential thrombocythemia (ET) and 29 myelofibrosis (MF)]. CALR-mutated ET patients harbored a higher mutant load at progenitor level than JAK2V617F-positive ET (HSCs: 39.9% vs 7.5% p<0.001, HPCs: 32.7% vs 7.7% p<0.001). Moreover, HSCs of CALR-mutated ET patients showed a similar mutational load than patients with CALR-mutated MF (39.9% vs 48.2%, p=0.17). Regarding JAK2V617F MPN, PV and ET patients showed a low mutational burden at progenitor level whereas in the myelofibrotic phase the dominance of the mutated clone was a constant finding. In conclusion, the size of the mutated clone in chronic phase MPN is different according to genotype with CALR-mutated ET showing a pattern similar to that observed in MF.
authors.affiliation: Hematology Department, Hospital del Mar, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain; Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Angona
authors.affiliation: Hematology Department, Hospital del Mar, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain; Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain. Electronic address: 95967@parcdesalutmar.cat.
authors.forename: Alberto
authors.initials: A
authors.lastname: Alvarez-Larrán
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain; Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Longarón
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain; Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Camacho
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain; Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: M Concepción
authors.initials: MC
authors.lastname: Fernández-Rodríguez
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain; Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pairet
authors.affiliation: Hematology Department, Hospital del Mar, Barcelona, Spain; Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Besses
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34; D037282:Calreticulin / Q000235:genetics*; D002999:Clone Cells; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D011087:Polycythemia Vera / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D037282:Calreticulin; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Allele burden; CALR; Hematopoietic stem cells; JAK2V617F; Myeloproliferative neoplasms