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The Leukemia-Initiating Cell: Genetic Determinants, Escape Mechanisms and Ontogenic Influence

Objective

Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults and strongly associated in incidence to advanced age. AML arises from immature hematopoietic progenitor cells via a sequential multistep process, but the nature of these steps remains to a large extent unknown. Therefore, while significant efforts have previously been invested in characterizing the molecular properties of late-stage AML, as diagnosed in patients, less information is available on the events that underlie leukemia initiation and progression. This includes the identity of potential mechanisms that restrict or eradicate developing leukemic cells; hurdles evaded at some point in time for AML to occur.
We have developed an inducible transgenic mouse model of AML that, when combined with high-resolution cell fractionation of primitive hematopoietic progenitor cells, offers a unique opportunity to track development of AML from the very first stages of cancer development. Using this, I propose to: 1) Identify and functionally validate molecular determinants that underlie why only some hematopoietic progenitor cells progress into AML, 2) To explore the extent and identity of immune surveillance/editing that accompany progression into AML, and 3) By building on my previous work on hematopoietic aging, to explore AML progression in the context of aging.
I anticipate the LEUKEMIABARRIER project to generate novel basic knowledge, not excluding with clinical relevance, with the potential to open up several new fields for further studies. This includes identification of novel cell-intrinsic regulators and immune responses, their underlying mechanisms, and their relationship to the increased incidence of AML with age.

Field of science

  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/clinical medicine/oncology/leukemia

Call for proposal

ERC-2013-CoG
See other projects for this call

Funding Scheme

ERC-CG - ERC Consolidator Grants

Host institution

MAX IV Laboratory, Lund University
Address
Paradisgatan 5C
22100 Lund
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 999 714
Principal investigator
David Bryder (Dr.)
Administrative Contact
Lhinn Skoog (Ms.)

Beneficiaries (1)

MAX IV Laboratory, Lund University
Sweden
EU contribution
€ 1 999 714
Address
Paradisgatan 5C
22100 Lund
Activity type
Higher or Secondary Education Establishments
Principal investigator
David Bryder (Dr.)
Administrative Contact
Lhinn Skoog (Ms.)