Splicing factor 3b subunit 1 Sf3b1 haploinsufficient mice display features of low risk Myelodysplastic syndromes with ring sideroblastsReportar como inadecuado

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Journal of Hematology and Oncology

, 7:89

First Online: 07 December 2014Received: 13 October 2014Accepted: 15 November 2014DOI: 10.1186-s13045-014-0089-x

Cite this article as: Visconte, V., Tabarroki, A., Zhang, L. et al. J Hematol Oncol 2014 7: 89. doi:10.1186-s13045-014-0089-x


BackgroundThe presence of somatic mutations in splicing factor 3b subunit 1 SF3B1 in patients with Myelodysplastic syndromes with ring sideroblasts MDS-RS highlights the importance of the RNA-splicing machinery in MDS. We previously reported the presence of bone marrow BM RS in Sf3b1 heterozygous Sf3b1 mice which are rarely found in mouse models of MDS. Sf3b1 mice were originally engineered to study the interaction between polycomb genes and other proteins.

MethodsWe used routine blood tests and histopathologic analysis of BM, spleen, and liver to evaluate the hematologic and morphologic characteristics of Sf3b1 mice in the context of MDS by comparing the long term follow-up 15 months of Sf3b1 and Sf3b1 mice. We then performed a comprehensive RNA-sequencing analysis to evaluate the transcriptome of BM cells from Sf3b1 and Sf3b1 mice.

ResultsSf3b1 exhibited macrocytic anemia MCV: 49.5 ± 1.6 vs 47.2 ± 1.4; Hgb: 5.5 ± 1.7 vs 7.2 ± 1.0 and thrombocytosis PLTs: 911.4 ± 212.1 vs 878.4 ± 240.9 compared to Sf3b1 mice. BM analysis showed dyserythropoiesis and occasional RS in Sf3b1 mice. The splenic architecture showed increased megakaryocytes with hyperchromatic nuclei, and evidence of extramedullary hematopoiesis. RNA-sequencing showed higher expression of a gene set containing Jak2 in Sf3b1 compared to Sf3b1.

ConclusionsOur study indicates that Sf3b1 mice manifest features of low risk MDS-RS and may be relevant for preclinical therapeutic studies.

KeywordsSF3B1 mice Myelodysplasia RNA-sequencing AbbreviationsSF3B1Splicing factor 3b, subunit 1

MDSMyelodysplastic syndromes

MDS-MPNMyelodysplastic- Myeloproliferative neoplasms

AMLAcute myeloid leukemia

MCVMean corpuscular volume


WBCWhite blood cells


RBCRed blood cells

RSRing sideroblasts

BMBone marrow

EMHExtramedullary hematopoiesis

JAK2Janus kinase 2

TET2Ten-eleven translocation-2

MPLMyeloproliferative leukemia virus oncogene

ALAS2Aminolevulinate, Delta-, Synthase 2

ABCB7ATP-binding cassette, sub-family B MDR-TAP, Member 7

U2AF65U2 small nuclear RNA auxiliary factor 2

SF3b14Splicing factor 3B, 14 kDa subunit

EZH2Enhancer of zeste homolog 2

RARSRefractory anemia with ring sideroblasts

RARS-TRefractory anemia with ring sideroblasts and marker thrombocytosis

PCRPolymerase chain reaction

HandEHematoxylin and Eosin

Electronic supplementary materialThe online version of this article doi:10.1186-s13045-014-0089-x contains supplementary material, which is available to authorized users.

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Autor: Valeria Visconte - Ali Tabarroki - Li Zhang - Yvonne Parker - Edy Hasrouni - Reda Mahfouz - Kyoichi Isono - Haruhiko Kosek

Fuente: https://link.springer.com/

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