Supplementary Figure S11 from Integrated genomic and transcriptomic analysis improves disease classification and risk stratification of MDS with ring sideroblasts.

Todisco, Gabriele; Creignou, Maria; Bernard, Elsa; Björklund, Ann-Charlotte; Moura, Pedro Luis.; Tesi, Bianca; Mortera Blanco, Teresa; Sander, Birgitta; Jansson, Monika; Walldin, Gunilla; Barbosa, Indira; Reinsbach, Susanne E.; Hofman, Isabel Juliana.; Nilsson, Christer; Yoshizato, Tetsuichi; Dimitriou, Marios; Chang, David; Olafsdottir, Svanhildur; Venckute Larsson, Sigita; Tobiasson, Magnus; Malcovati, Luca; Woll, Petter; Jacobsen, Sten-Eirik W.; Papaemmanuil, Elli; Hellström-Lindberg, Eva

doi:10.1158/1078-0432.27033784.v1

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Supplementary Figure S11 from Integrated genomic and transcriptomic analysis improves disease classification and risk stratification of MDS with ring sideroblasts.

journal contribution

posted on 2024-09-16, 11:34 authored by Gabriele Todisco, Maria Creignou, Elsa Bernard, Ann-Charlotte Björklund, Pedro Luis. Moura, Bianca Tesi, Teresa Mortera Blanco, Birgitta Sander, Monika Jansson, Gunilla Walldin, Indira Barbosa, Susanne E. Reinsbach, Isabel Juliana. Hofman, Christer Nilsson, Tetsuichi Yoshizato, Marios Dimitriou, David Chang, Svanhildur Olafsdottir, Sigita Venckute Larsson, Magnus Tobiasson, Luca Malcovati, Petter Woll, Sten-Eirik W. Jacobsen, Elli Papaemmanuil, Eva Hellström-Lindberg

ABCB7 expression throughout the spectrum of MDSRS+ genotypes. ABCB7 downregulation is restricted to SF3B1-mutant MDSRS+.

History

ARTICLE ABSTRACT

Purpose: Ring sideroblasts (RS) define the low-risk myelodysplastic neoplasm (MDS) subgroup with RS but may also reflect erythroid dysplasia in higher-risk myeloid neoplasm. The benign behavior of MDS with RS (MDSRS+) is limited to SF3B1-mutated cases without additional high-risk genetic events, but one third of MDSRS+ carry no SF3B1 mutation, suggesting that different molecular mechanisms may underlie RS formation. We integrated genomic and transcriptomic analyses to evaluate whether transcriptome profiles may improve current risk stratification. Experimental design: We studied a prospective cohort of MDSRS+ patients irrespective of WHO class with regard to somatic mutations, copy number alterations and bone marrow CD34+ cell transcriptomes to assess whether transcriptome profiles add to prognostication and provide input on disease classification. Results: SF3B1, SRSF2 or TP53 multi-hit (MH) mutations were found in 89% of MDSRS+ cases, and each mutation category was associated with distinct clinical outcome, gene expression, and alternative splicing profiles. Unsupervised clustering analysis identified three clusters with distinct hemopoietic stem and progenitor (HSPC) composition, which only partially overlapped with mutation groups. IPSS-M and the transcriptome-defined proportion of megakaryocyte/erythroid progenitors (MEP) independently predicted survival in multivariable analysis. Conclusion: These results provide essential input on the molecular basis of SF3B1-unmutated MDSRS+ and propose HSPC quantification as a prognostic marker in myeloid neoplasms with RS.