High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS)

Abstract

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.

Targeted deep sequencing of CD34+ cells from peripheral blood can reproduce bone marrow molecular profile in myelodysplastic syndromes

“…Decreased VAF values in PB were also reported by Mohamedali et al4 However, the differences were not statistically significant. The significant deviation that we observed potentially resulted from a more stringent removal of SNPs in our dataset due to the analysis of the germline sample (CD3 + ).…”

“…For non‐enriched PB, this was previously shown,4 while in the current study we have added PB‐CD34. We were able to detect 93/105 mutations (89%) in all sample types (BMC, PB‐CD34, and PB‐MC) (Supporting Information Table S5).…”

Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation

“…The exact reasons for this apparent discrepancy were unknown, but most likely to be explained by different cell sources, sampling time, and target cell population, as well as the difference in sensitivity between assays. [38][39][40] Thus, taking this into consideration, most of the TP53-mutated cases had a CK or a CK-like abnormality, together with accompanying 17pLOH and del(5q). 27/del(7q) has also been closely associated with a CK, which was also confirmed by sequencing-based copy-number profiling (n 5 47).…”

Mutational landscape and response are conserved in peripheral blood of AML and MDS patients during decitabine therapy

“…10 Other groups have observed concordant PB NPM1 mutation clearance and PB copy number abnormalities [11][12][13][14] and have occasionally used PB for mutation discovery. [15][16][17] Therefore, we sought to compare the mutation burden in paired serial PB and BM samples in patients with AML or MDS to determine whether sequencing of PB samples is a viable approach for determining clonal architecture and whether it might provide an adjunct, and less invasive, measure of response to therapy.…”