Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023418 (
leukemia
)
93,477
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The cell of origin, defined as the normal cell in which the transformation event first occurs, is poorly identified in
leukemia
, despite its importance in understanding of leukemogenesis and improving
leukemia
therapy. Although hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were used for
leukemia
models, whether their self-renewal and differentiation potentials influence the initiation and development of
leukemia
is largely unknown. In this study, the self-renewal and differentiation potentials in 2 distinct types of HSCs (HSC1 [CD150
+
CD41
-
CD34
-
Lineage
-
Sca-1
+
c-Kit
+
cells] and HSC2 [CD150
-
CD41
-
CD34
-
Lineage
-
Sca-1
+
c-Kit
+
cells]) and 3 distinct types of HPCs (HPC1 [CD150
+
CD41
+
CD34
-
Lineage
-
Sca-1
+
c-Kit
+
cells], HPC2 [CD150
+
CD41
+
CD34
+
Lineage
-
Sca-1
+
c-Kit
+
cells], and
HPC3
[CD150
-
CD41
-
CD34
+
Lineage
-
Sca-1
+
c-Kit
+
cells]) were isolated from adult mouse bone marrow, and examined by competitive repopulation assay. Then, cells from each population were retrovirally transduced to initiate MLL-AF9 acute myelogenous leukemia (AML) and the intracellular domain of NOTCH-1 T-cell acute lymphoblastic leukemia (T-ALL). AML and T-ALL similarly developed from all HSC and HPC populations, suggesting multiple cellular origins of
leukemia
. New leukemic stem cells (LSCs) were also identified in these AML and T-ALL models. Notably, switching between immunophenotypical immature and mature LSCs was observed, suggesting that heterogeneous LSCs play a role in the expansion and maintenance of
leukemia
. Based on this mouse model study, we propose that acute leukemia arises from multiple cells of origin independent of the self-renewal and differentiation potentials in hematopoietic stem and progenitor cells and is amplified by LSC switchover.
...
PMID:Mouse acute leukemia develops independent of self-renewal and differentiation potentials in hematopoietic stem and progenitor cells. 3073 2
