High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS).
Bone marrow (BM) genetic abnormalities in myelodysplastic syndrome (MDS) have provided important biological and prognostic information; however, frequent BM sampling in older patients has been associated with significant morbidity. Utilizing single-nucleotide polymorphism array (SNP-A) and targeted gene sequencing (TGS) of 24 frequently mutated genes in MDS, we assessed the concordance of genetic abnormalities in BM and peripheral blood (PB) samples concurrently from 201 MDS patients. SNP-A karyotype in BM was abnormal in 108 (54%) and normal in 93 (46%) patients, with 95% (190/201) having an identical PB karyotype. The median copy number (CN) for deletions was significantly lower in BM (CN:1.4 (1-1.9)) than in PB (CN:1.5 (1-1.95), P<0.001). Using TGS, 71% (130/183) patients had BM somatic mutations with 95% (124/130) having identical mutations in PB. The mutant allele burden was lower in PB (median 27% (1-96%)) compared with BM (median 29% (1-100%); P=0.14) with no significant difference in the number, types of mutations or World Health Organization subtype. In all patients with discordant SNP (n=11) and mutation (n=6) profiles between BM and PB, shared abnormalities were always present irrespective of treatment status. Overall, 86% of patients had a clonal aberration with 95% having identical SNP-A karyotype and mutations in PB, thus enabling frequent assessment of response to treatment and disease evolution especially in patients with fibrotic or hypocellular marrows.
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.|Department of Haematology, King's College Hospital, Department of Haematology, London, UK.
A M
AM
Mohamedali
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.
J
J
Gäken
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.|Department of Haematology, King's College Hospital, Department of Haematology, London, UK.
M
M
Ahmed
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.
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F
Malik
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.|Department of Haematology, King's College Hospital, Department of Haematology, London, UK.
A E
AE
Smith
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.|Department of Haematology, King's College Hospital, Department of Haematology, London, UK.
S
S
Best
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.
S
S
Mian
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.|Department of Haematology, King's College Hospital, Department of Haematology, London, UK.
T
T
Gaymes
Department of Haematology, King's College Hospital, Department of Haematology, London, UK.
R
R
Ireland
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.|Department of Haematology, King's College Hospital, Department of Haematology, London, UK.
A G
AG
Kulasekararaj
Department of Haematological Medicine, The Rayne Institute, King's College London School of Medicine, London, UK.|Department of Haematology, King's College Hospital, Department of Haematology, London, UK.
G J
GJ
Mufti
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000378:metabolism* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002869:Chromosome Aberrations; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D023281:Genomics; D006801:Humans; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult