Impact of allogeneic hematopoietic cell transplant in patients with myeloid neoplasms carrying spliceosomal mutations

American Journal of Hematology
Betty K HamiltonRamon V Tiu

Abstract

Molecular predictors of outcome are increasingly important in determining optimal therapy for myeloid neoplasms. Mutations in the spliceosomal genes (U2AF1 and SRSF2) predict for poor outcomes in myelodysplastic syndromes (MDS) and related diseases. We investigated the effect of hematopoietic cell transplant (HCT) on the negative prognostic impact of U2AF1 and SRSF2 mutations. In total, 122 patients with MDS (30%), acute myeloid leukemia (51%), myeloproliferative neoplasms (MPN) (11%), and MDS/MPN (8%) receiving a HCT from 2003 to 2012 were evaluated for mutations in U2AF1 and SRSF2 by direct sequencing. Median time of follow up was 24 months (range 0.46-110). SRSF2 mutations were detected in 11 (10%) patients and U2AF1 in 3 (3%) patients. There were no significant differences in baseline characteristics between mutated and wild-type (WT) patients. Patients carrying SRSF2 and U2AF1 mutations had similar overall survival (P = 0.84), relapse mortality (P = 0.50), and non-relapse mortality (P = 0.72) compared to WT patients. However, taking into account disease status and cytogenetics in a subset of AML patients, SRSF2 and U2AF1 mutations were associated with worse survival (HR 3.71, P = 0.035).

References

Nov 26, 2010·The New England Journal of Medicine·Ted A GooleyGeorge B McDonald
Jul 1, 2011·The New England Journal of Medicine·Rafael BejarBenjamin L Ebert
Oct 15, 2011·The New England Journal of Medicine·E PapaemmanuilUNKNOWN Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium
Dec 14, 2011·Nature Genetics·Timothy A GraubertMatthew J Walter
Jan 4, 2012·International Journal of Laboratory Hematology·P L Greenberg
Jan 27, 2012·Current Hematologic Malignancy Reports·Giovanni BarosiVittorio Rosti
Mar 16, 2012·The New England Journal of Medicine·Matthew J WalterTimothy A Graubert
May 3, 2013·The New England Journal of Medicine·UNKNOWN Cancer Genome Atlas Research NetworkGreg Eley
Sep 14, 2013·Blood·Elli PapaemmanuilUNKNOWN Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium
Aug 6, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rafael BejarBenjamin L Ebert

❮ Previous
Next ❯

Citations

Mar 15, 2019·Journal of Internal Medicine·M Tobiasson, A O Kittang
Jul 24, 2020·Scientific Reports·Shujuan WangYanfang Liu
Jul 22, 2021·American Journal of Hematology·Juliane GrimmSebastian Schwind
Nov 13, 2017·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Rachel B Salit, H Joachim Deeg

❮ Previous
Next ❯

Related Concepts

Related Feeds

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.