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The route to development of myelodysplastic syndrome/acute myeloid leukaemia in Shwachman-Diamond syndrome: the role of ageing, karyotype instability, and acquired chromosome anomalies
- Publication Year :
- 2009
-
Abstract
- Summary 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.
- Subjects :
- Myeloid
Male
Pathology
Aging
DNA Mutational Analysis
Chromosomes, Human, Pair 20
hemic and lymphatic diseases
genetics
Child
In Situ Hybridization, Fluorescence
In Situ Hybridization
Chromosome 7 (human)
Shwachman–Diamond syndrome
Acute leukemia
Leukemia
Shwachman-Diamond syndrome
Karyotype
Chromosome Breakage
Hematology
ultrastructure
Leukemia, Myeloid, Acute
Child, Preschool
Disease Progression
Pair 7
Female
Chromosomes, Human, Pair 7
Human
Adult
acute leukaemia
medicine.medical_specialty
Adolescent, Adult, Aging
genetics, Bone Marrow Cells
ultrastructure, Child, Child
Preschool, Chromosome Aberrations, Chromosome Breakage, Chromosomes
Pair 20, Chromosomes
Pair 7, DNA Mutational Analysis, Disease Progression, Female, Follow-Up Studies, Humans, In Situ Hybridization
Fluorescence, Isochromosomes, Karyotyping, Leukemia
Acute
genetics, Male, Myelodysplastic Syndromes
genetics, Proteins
genetics, Young Adult
Adolescent
myelodysplastic syndrome
karyotype instability
ageing
Isochromosome
Bone Marrow Cells
Biology
Chromosomes
Fluorescence
Young Adult
medicine
Humans
Preschool
Chromosome Aberrations
Myelodysplastic syndromes
Cytogenetics
Chromosome
Proteins
medicine.disease
Molecular biology
Isochromosomes
Karyotyping
Myelodysplastic Syndromes
Pair 20
Follow-Up Studies
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....a1ca10003ec63556158e5f783b18d6fd