Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS)

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, than those with NH-MDS. h-MDS was closely associated with lower-risk MDS, defined by the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R). IPSS-R could properly predict the prognosis in h-MDS (P<0.001) as in NH-MDS patients. The h-MDS patients had lower incidences of RUNX1, ASXL1, DNMT3A, EZH2 and TP53 mutations than NH-MDS patients. The cumulated incidence of acute leukemic transformation at 5 years was 19.3% for h-MDS and 40.4% for NH-MDS patients (P= 0.001). Further, the patients with h-MDS had longer overall survival (OS) than those with NH-MDS (P= 0.001), and BM hypocellularity remains an independent favorable prognostic factor for OS irrespective of age, IPSS-R, and gene mutations. Our findings provide evidence that h-MDS indeed represent a distinct clinico-biological subgroup of MDS and can predict better leukemia-free survival and OS.

Mutations and karyotype predict treatment response in myelodysplastic syndromes

“…Targeted capture assays were carried out, on bone marrow DNA specimens, for the following genes: TET2 , DNMT3A , IDH1 , IDH2 , ASXL1 , EZH2 , SUZ12 , SRSF2 , SF3B1 , ZRSR2 , U2AF1 , PTPN11 , TP53 , SH2B3 , RUNX1 , CBL , NRAS , JAK2 , CSF3R , FLT3 , KIT , CALR , MPL , NPM1 , CEBPA , IKZF1 and SETBP1. Further details on mutation screening have been previously published and detailed in the supplement . A retrospective chart review was conducted in 357 consecutive patients with primary MDS.…”

Clinico-pathological spectrum and novel karyotypic findings in myelodysplastic syndrome: Experience of tertiary care centre in India

“… 22 , 23 In a recent study of 100 hypoplastic MDS patients, it was observed that these patients have statistically significant lower peripheral blood counts, bone marrow blast percentages and a lower incidence of poor-risk cytogenetic abnormalities, as compared to the non hypoplastic groups. 24 On the contrary, in our cohort of 9.3% (14/150) patients with hypoplastic MDS, the median blast count was 5% and 78% (7/9) of these patients were found to harbor abnormal karyotype ( Supplementary table 2 ).…”

Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

“…Table 2 recapitulates the main cytogenetic and molecular aspects of normo/hypercellular MDS, hMDS, and AA. Since cytogenetic studies [ 6 , 12 , 15 , 16 ] showed no remarkable differences between non-hMDS and hMDS, although the latter more frequently show lower-risk karyotypes, the resolution achieved by molecular approaches may be particularly valuable. High-throughput next-generation sequencing (NGS) characterization represents a powerful tool to detect eventually ontogenetic and prognostic features distinctive of hMDS.…”

“…An initial study from Huang et al compared 37 hMDS patients to 152 non-hMDS patients of a single-center Taiwanese cohort, without scoring any significant difference in the prevalence of RAS, AML1, JAK2, PTPN11, and FLT3/ITD mutations [ 12 ]. More recently, two single-center studies [ 15 , 16 ] investigated selected gene mutations of known importance in myeloid disorders, comparing their prevalence in hMDS vs. non-hMDS patients. Nahza et al showed that hMDS was associated with fewer somatic mutations and smaller driver clones compared to non-hMDS (including both normo- and hypercellular MDS).…”