Advanced

High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.

Quere, Ronan LU ; Andradottir, Silja LU ; Brun, Ann; Zubarev, R A; Karlsson, Göran LU ; Olsson, Karin LU ; Magnusson, Mattias LU ; Cammenga, Jörg LU and Karlsson, Stefan LU (2011) In Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 25. p.515-526
Abstract
Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite... (More)
Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia.Leukemia advance online publication, 30 November 2010; doi:10.1038/leu.2010.281. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
volume
25
pages
515 - 526
publisher
Nature Publishing Group
external identifiers
  • WOS:000288159500015
  • PMID:21116281
  • Scopus:79952448517
ISSN
1476-5551
DOI
10.1038/leu.2010.281
language
English
LU publication?
yes
id
69ad4541-8126-4703-861f-a54b4545606c (old id 1756957)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21116281?dopt=Abstract
date added to LUP
2011-01-03 09:42:32
date last changed
2016-11-13 04:28:30
@misc{69ad4541-8126-4703-861f-a54b4545606c,
  abstract     = {Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia.Leukemia advance online publication, 30 November 2010; doi:10.1038/leu.2010.281.},
  author       = {Quere, Ronan and Andradottir, Silja and Brun, Ann and Zubarev, R A and Karlsson, Göran and Olsson, Karin and Magnusson, Mattias and Cammenga, Jörg and Karlsson, Stefan},
  issn         = {1476-5551},
  language     = {eng},
  pages        = {515--526},
  publisher    = {ARRAY(0xb6db360)},
  series       = {Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K},
  title        = {High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.},
  url          = {http://dx.doi.org/10.1038/leu.2010.281},
  volume       = {25},
  year         = {2011},
}