Distinct bone marrow immunophenotypic features define the splicing factor 3B subunit 1 (SF3B1)-mutant myelodysplastic syndromes subtype

Abstract

Splicing factor 3B subunit 1 (SF3B1) mutations define a distinct myelodysplastic syndromes (MDS) patient group with a relatively favourable disease course and high response rates to luspatercept. Few data are available on bone marrow phenotype beyond ring sideroblasts in this subgroup of patients with MDS. In the present study, we identified immunophenotypic erythroid, myelomonocyte and progenitor features associated with SF3B1 mutations. In addition, we illustrate that SF3B1-mutation type is associated with distinct immunophenotypic features, and show the impact of co-occurrence of a SF3B1 mutation and a deletion of chromosome 5q on bone marrow immunophenotype. These genotype-phenotype associations and phenotypic subtypes within SF3B1-MDS provide leads that may further refine prognostication and therapeutic strategies for this particular MDS subgroup.

Keywords: SF3B1; diagnostic haematology; flow cytometry; mutational analysis; myelodysplastic syndromes.

Fig 1

Immunophenotypic features associated with splicing factor 3B subunit 1‐myelodysplastic syndromes (SF3B1‐MDS) subtype. Patients within the SF3B1‐MDS subtype (SF3B1‐MDS) displayed immunophenotypic features that differed significantly from SF3B1 wild‐type MDS (Other‐MDS) and controls (non‐cytopenic and age‐matched). Multiple bone marrow cell subsets (A), erythroid features (B) and myelomonocytic features (C) were associated with the SF3B1‐MDS subtype. Erythroid progenitors were defined as CD36 and CD71 positive, myeloid progenitors as CD34 and CD117 positive, neutrophils as CD45^dim, side scatter (SSC) medium‐high and CD34 negative, monocytes as CD45 high, SSC medium and CD11b, CD14 and CD36 positivity. Cell population percentages were calculated relative to total bone marrow white blood cell, with the exception of erythroid progenitors that were calculated relative to total nucleated cells. Antigen expression levels [both CVs and MFIs (on the y‐axis)] were expressed relative to expression of controls. ¹⁵ The Mann–Whitney U‐test was applied for the comparisons. *P < 0·05, **P < 0·01, ***P < 0·001. CV, coefficient of variation; dim, diminished; MFI, mean fluorescent intensity; SSC, sideward light scatter.

Fig 2

Immunophenotypic features in patients with del(5q), splicing factor 3B subunit 1‐myelodysplastic syndromes (SF3B1‐MDS) subtype, and patients with both genetic lesions. Immunophenotypic features significantly different between patients with the SF3B1‐MDS subtype and patients with del(5q) were identified. Panel A, shows that of those features, six – concerning erythroid cells, myeloid progenitors and lymphocytes – were significantly different between patients with an isolated SF3B1‐MDS subtype and patients with both a del(5q) and SF3B1‐MDS. Panel B, shows that four other features – concerning maturing monocytes and neutrophils – were significantly different between del(5q) and patients with both a del(5q) and SF3B1‐MDS subtype. Erythroid progenitors were defined as CD36 and CD71 positive, myeloid progenitors as CD34 and CD117 positive, neutrophils as CD45^dim, side scatter (SSC) medium‐high and CD34 negative, monocytes as CD45 high, SSC medium and CD11b, CD14 and CD36 positivity. Population sizes were calculated relative to total bone marrow white blood cell, with the exception of erythroid progenitors that were calculated relative to total nucleated cells. Expression levels both CVs and MFIs (on the y‐axis) were shown relative to expression of controls. ¹⁵ The Mann–Whitney U‐test was applied for the comparisons. *P < 0·05, **P < 0·01, ***P < 0·001. CV, coefficient of variation; dim, diminished; MFI, mean fluorescent intensity; SSC, sideward light scatter.