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:C0023473 (
chronic myeloid leukemia
)
18,916
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tyrosine kinase inhibitor treatment of
chronic myeloid leukemia
(
CML
) has demonstrated beneficial effects. However, resistance to tyrosine kinase inhibitors and disease relapse are still a challenge for
CML
therapy. In this study, we analyzed bone marrow samples from 149
CML
patients and 15 control donors, and investigated the affect of AF1q on
CML
cell survival and engraftment in vitro and in vivo. We found that AF1q/
MLLT11
expression was significantly upregulated in
CML
patients, especially in CD34
+
CML
cells. Elevated AF1q expression was associated with disease progression. Knockdown of AF1q enhanced imatinib sensitivity, induced apoptosis, and suppressed growth in
CML
cells. Moreover, AF1q deficiency sensitized CD34
+
CML
cells to imatinib. In contrast, upregulation of AF1q promoted cell survival, protected
CML
cells from imatinib-induced apoptosis, and increased engraftment of
CML
cells in vivo. We further identified a positive correlation between AF1q and CD44 expression in chronic phase CML patients and CD34
+
CML
cells. Importantly, AF1q contributes to imatinib-resistance in
CML
by regulating the expression of CD44. These findings reveal a novel BCR-ABL-independent pathway, AF1q/CD44, involves imatinib resistance in
CML
, thus representing a potential therapeutic target for imatinib-resistant
CML
patients.
...
PMID:Novel AF1q/MLLT11 favorably affects imatinib resistance and cell survival in chronic myeloid leukemia. 3015 35
