title: Newly diagnosed adult AML and MPAL patients frequently show clonal residual hematopoiesis.
abstract: Adult acute myeloid leukemia (AML) is a highly heterogeneous stem cell malignancy characterized by the clonal expansion of immature myeloid precursors. AML may emerge de novo, following other hematopoietic malignancies or after cytotoxic therapy for other disorders. Here, we investigated the clonal vs reactive nature of residual maturing bone marrow cells in 59 newly diagnosed adult AML and mixed phenotype acute leukemia (MPAL) patients as assessed by interphase fluorescence in situ hybridization analysis of AML and myelodysplastic syndrome-associated cytogenetic alterations and/or the pattern of chromosome X inactivation, in females. In addition, we investigated the potential association between the degree of molecular/genetic involvement of hematopoiesis and coexistence of altered immunophenotypes by flow cytometry. Our results indicate that residual maturing neutrophils, monocytes and nucleated red cell precursors from the great majority of newly diagnosed AML and MPAL cases show a clonal pattern of involvement of residual maturing hematopoietic cells, in association with a greater number of altered immunophenotypes. These findings are consistent with the replacement of normal/reactive hematopoiesis by clonal myelopoiesis and/or erythropoiesis in most newly diagnosed AML and MPAL cases, supporting the notion that in most adults presenting with de novo AML, accumulation of blast cells could occur over a pre-existing clonal hematopoiesis.
authors.affiliation: Servicio General de Citometría and Departamento de Medicina, Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer and IBSAL; CSIC-USAL), Universidad de Salamanca, Salamanca, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Fernandez
authors.forename: M C
authors.initials: MC
authors.lastname: Santos-Silva
authors.forename: A
authors.initials: A
authors.lastname: López
authors.forename: S
authors.initials: S
authors.lastname: Matarraz
authors.forename: M
authors.initials: M
authors.lastname: Jara-Acevedo
authors.forename: J
authors.initials: J
authors.lastname: Ciudad
authors.forename: M L
authors.initials: ML
authors.lastname: Gutierrez
authors.forename: M L
authors.initials: ML
authors.lastname: Sánchez
authors.forename: C
authors.initials: C
authors.lastname: Salvador-Osuna
authors.forename: M J
authors.initials: MJ
authors.lastname: Berruezo
authors.forename: J Á
authors.initials: JÁ
authors.lastname: Díaz-Arias
authors.forename: A M
authors.initials: AM
authors.lastname: Palomo-Hernández
authors.forename: E
authors.initials: E
authors.lastname: Colado
authors.forename: N
authors.initials: N
authors.lastname: González
authors.forename: D
authors.initials: D
authors.lastname: Gallardo
authors.forename: A
authors.initials: A
authors.lastname: Asensio
authors.forename: R
authors.initials: R
authors.lastname: García-Sánchez
authors.forename: R
authors.initials: R
authors.lastname: Saldaña
authors.forename: C
authors.initials: C
authors.lastname: Cerveró
authors.forename: A
authors.initials: A
authors.lastname: Carboné-Bañeres
authors.forename: O
authors.initials: O
authors.lastname: Gutierrez
authors.forename: A
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006410:Hematopoiesis; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015456:Leukemia, Biphenotypic, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics
chemical_list: D019009:Proto-Oncogene Proteins c-kit