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MLL1 plays an essential role in steady-state hematopoiesis and B Lymphopoiesis / by Tao Gan.

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Author	Gan, Tao.
Title	MLL1 plays an essential role in steady-state hematopoiesis and B Lymphopoiesis / by Tao Gan.
Date	2014
Abstract	The Mixed Lineage Leukemia (MLL1) gene was first cloned as a hot spot of chromosomal translocations in acute leukemia. More than 70 fusion proteins of MLL1 have been described in both lymphoid and myeloid leukemia and many are highly associated with poor prognosis. Loss-of-function studies of MLL1 revealed an intrinsic requirement for MLL1 in the maintenance of stem/progenitor populations. However, controversy remains regarding whether MLL1 plays a role in steady-state hematopoiesis postnatally. A developmentally-induced deletion of MLL1 revealed phenotypically normal fetal hematopoiesis, but lethality within 3 weeks after birth. Loss of stem/progenitor populations led to severely impaired steady-state hematopoiesis in VavCre;MLL1 mutant mice. Furthermore, a selective reduction of B cells was observed upon loss of MLL1. Lymphoid specific deletion of MLL1 recapitulated the selective B cell defects. Early B cell development was partially blocked at the pro-to pre-B transition stage in MLL1-deficient mice. Survival of developing B cells promoted by pre-BCR signal was significantly decreased in the absence of MLL1, which has been linked to attenuated RAS-ERK signaling likely due elevated expression of Let-7a. Overall, data presented in this work strongly support critical functions performed by MLL1 during adult steady-state hematopoiesis and B lymphopoiesis which might provide significant insight into molecular pathways deregulated by MLL1 fusion oncogene and furthermore therapeutic targeting approaches for leukemia treatment, especially in the case of B-acute lymphoblastic leukemia (ALL).
Description	xi, 166 leaves : ill. (some col.)
Format	application/pdf
College	Dartmouth Medical School. Department of Genetics.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1231

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MLL1 plays an essential role in steady-state hematopoiesis and B Lymphopoiesis / by Tao Gan.

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