title: The route to development of myelodysplastic syndrome/acute myeloid leukaemia in Shwachman-Diamond syndrome: the role of ageing, karyotype instability, and acquired chromosome anomalies.
abstract: An investigation of 22 new patients with Shwachman-Diamond syndrome (SDS) and the follow-up of 14 previously reported cases showed that (i) clonal chromosome changes of chromosomes 7 and 20 were present in the bone marrow (BM) of 16 out of 36 cases, but if non-clonal changes were taken into account, the frequency of anomalies affecting these chromosomes was 20/36: a specific SDS karyotype instability was thus confirmed; (ii) the recurrent isochromosome i(7)(q10) did not include short arm material, whereas it retained two arrays of D7Z1 alphoid sequences; (iii) the deletion del(20)(q11) involved the minimal region of deletion typical of myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML); (iv) only one patient developed MDS, during the rapid expansion of a BM clone with a chromosome 7 carrying additional material on the short arms; (v) the acquisition of BM clonal chromosome anomalies was age-related. We conclude that karyotype instability is part of the natural history of SDS through a specific mutator effect, linked to lacking SBDS protein, with consequent clonal anomalies of chromosomes 7 and 20 in BM, which may eventually promote MDS/AML with the patients' ageing.
authors.affiliation: Biologia e Genetica, Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università dell'lnsubria, Varese, Italy. emanuela.maserati@uninsubria.it
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maserati
authors.forename: Barbara
authors.initials: B
authors.lastname: Pressato
authors.forename: Roberto
authors.initials: R
authors.lastname: Valli
authors.forename: Antonella
authors.initials: A
authors.lastname: Minelli
authors.forename: Laura
authors.initials: L
authors.lastname: Sainati
authors.forename: Francesco
authors.initials: F
authors.lastname: Patitucci
authors.forename: Cristina
authors.initials: C
authors.lastname: Marletta
authors.forename: Angela
authors.initials: A
authors.lastname: Mastronuzzi
authors.forename: Furio
authors.initials: F
authors.lastname: Poli
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Curto
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasquali
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000235:genetics*; D001854:Bone Marrow Cells / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002890:Chromosomes, Human, Pair 20; D002897:Chromosomes, Human, Pair 7; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018404:Isochromosomes; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D011506:Proteins; C470521:SBDS protein, human