Clinical and molecular characteristics of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion

Haematologica
Kentaro OhkiTokyo Children’s Cancer Study Group (TCCSG)

Abstract

Fusion genes involving MEF2D have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remain unknown. We identified 16 cases of acute lymphoblastic leukemia and 1 of lymphoma harboring MEF2D fusions, including MEF2D-BCL9 (n=10), MEF2D-HNRNPUL1 (n=6), and one novel MEF2D-HNRNPH1 fusion. The incidence of MEF2D fusions overall was 2.4% among consecutive precursor B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial. They frequently showed a cytoplasmic μ chain-positive pre-B immunophenotype, and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of HDAC9 and MEF2C, elevated GATA3 expression was also a characteristic feature of MEF2D fusion-positive patients. Mutations of PHF6, recurrent in T-cell acute lymphoblastic leukemia, also showed an unexpectedly high frequency (50%) in these patients. MEF2D fusion-positive patients were older (median age 9 years) with elevated WBC counts (median: 27,300/ml) at presentation and, as a result, were mostly classified as NCI high risk. Although they responded well to steroid treat...Continue Reading

Citations

Jun 10, 2020·Hematological Oncology·Koshi AkahaneTakeshi Inukai
Oct 28, 2019·Cold Spring Harbor Perspectives in Medicine·Kathryn G Roberts, Charles G Mullighan
Feb 29, 2020·Blood Cancer Journal·Daiichiro HasegawaUNKNOWN Japan Association of Childhood Leukemia Study Group (JACLS)
Nov 30, 2019·Annals of Hematology·Jiewen SunXiang Zhang
Jun 17, 2020·Therapeutic Advances in Hematology·Seth E Karol, Ching-Hon Pui
Nov 23, 2020·Protein Expression and Purification·Zhiming ChenGuoyu Meng
Oct 16, 2020·Haematologica·Hiroto Inaba, Charles G Mullighan
Nov 26, 2020·Journal of Pediatric Hematology/oncology·Hee Jo BaekHoon Kook
May 6, 2021·Journal of Clinical Medicine·Hiroto Inaba, Ching-Hon Pui
Aug 13, 2021·Frontiers in Oncology·Jason H Kurzer, Olga K Weinberg
Dec 8, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ga Hye Kim, Ilmin Kwon

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
PCA

Software Mentioned

Prism
Gene Mapper
GraphPad
GSEA

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

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.