title: Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuria.
abstract: Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by the expansion of a haematopoietic stem cell clone with a PIG-A mutation (the PNH clone) in an environment in which normal stem cells are lost or failing: it has been hypothesized that this abnormal marrow environment provides a relative advantage to the PNH clone. In patients with PNH, generally, the karyotype of bone marrow cells has been reported to be normal, unlike in myelodysplastic syndrome (MDS), another clonal condition in which cytogenetic abnormalities are regarded as diagnostic. In a retrospective review of 46 patients with a PNH clone, we found a karyotypic abnormality in 11 (24%). Upon follow-up, the proportion of cells with abnormal karyotype decreased significantly in seven of these 11 patients. Abnormal morphological bone marrow features reminiscent of MDS were common in PNH, regardless of the karyotype. However, none of our patients developed excess blasts or leukaemia. We conclude that in patients with PNH cytogenetically abnormal clones are not necessarily malignant and may not be predictive of evolution to leukaemia.
authors.affiliation: Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Araten
authors.forename: D
authors.initials: D
authors.lastname: Swirsky
authors.forename: A
authors.initials: A
authors.lastname: Karadimitris
authors.forename: R
authors.initials: R
authors.lastname: Notaro
authors.forename: K
authors.initials: K
authors.lastname: Nafa
authors.forename: M
authors.initials: M
authors.lastname: Bessler
authors.forename: H T
authors.initials: HT
authors.lastname: Thaler
authors.forename: H
authors.initials: H
authors.lastname: Castro-Malaspina
authors.forename: B H
authors.initials: BH
authors.lastname: Childs
authors.forename: F
authors.initials: F
authors.lastname: Boulad
authors.forename: M
authors.initials: M
authors.lastname: Weiss
authors.forename: N
authors.initials: N
authors.lastname: Anagnostopoulos
authors.forename: A
authors.initials: A
authors.lastname: Kutlar
authors.forename: D G
authors.initials: DG
authors.lastname: Savage
authors.forename: R T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: S
authors.initials: S
authors.lastname: Jhanwar
authors.forename: L
authors.initials: L
authors.lastname: Luzzatto
mesh_terms: D000293:Adolescent; D000328:Adult; D002869:Chromosome Aberrations; D005260:Female; D005500:Follow-Up Studies; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D016896:Treatment Outcome