title: Myelodysplasia in autosomal dominant and sporadic monocytopenia immunodeficiency syndrome: diagnostic features and clinical implications.
abstract: A novel, genetic immunodeficiency syndrome has been recently described, herein termed "MonoMAC". It is characterized by severe circulating monocytopenia, NK- and B-lymphocytopenia, severe infections with M. avium complex (MAC), and risk of progression to myelodysplasia/acute myelogenous leukemia. Detailed bone marrow analyses performed on 18 patients further define this disorder. The majority of patients had hypocellular marrows with reticulin fibrosis and multilineage dysplasia affecting the myeloid (72%), erythroid (83%) and megakaryocytic (100%) lineages. Cytogenetic abnormalities were present in 10 of 17 (59%). Despite B-lymphocytopenia, plasma cells were present but were abnormal (e.g. CD56(+)) in nearly half of cases. Increased T-cell large granular lymphocyte populations were present in 28% of patients. Chromosomal breakage studies, cell cycle checkpoint functions, and sequencing of TERT and K-RAS genes revealed no abnormalities. MonoMAC appears to be a unique, inherited syndrome of bone marrow failure. We describe distinctive bone marrow features to help in its recognition and diagnosis. (Clinicaltrials.gov identifiers: NCT00018044, NCT00923364, NCT01212055).
authors.affiliation: Hematology Section, Department of Laboratory Medicine, NIH Clinical Center, 10 Center Dr., Bethesda, MD 20892-1508, USA. calvok@mail.nih.gov
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Calvo
authors.forename: Donald C
authors.initials: DC
authors.lastname: Vinh
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.forename: Weixin
authors.initials: W
authors.lastname: Wang
authors.forename: Pierre
authors.initials: P
authors.lastname: Noel
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Diane C
authors.initials: DC
authors.lastname: Arthur
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Amalia
authors.initials: A
authors.lastname: Dutra
authors.forename: Evgenia
authors.initials: E
authors.lastname: Pak
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Myung
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D020732:Cytogenetic Analysis; D018450:Disease Progression; D005260:Female; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000175:diagnosis*; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D007970:Leukopenia / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000473:pathology; D012306:Risk; D055815:Young Adult