Relation between CXCR-4 expression, Flt3 mutations and unfavourable prognosis of adult acute myeloid leukemia
| Autor: | Biljana Pavic, Elwin J. C. Rombouts, Bob Löwenberg, Rob E. Ploemacher |
|---|---|
| Přispěvatelé: | Hematology |
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Receptors CXCR4 Myeloid Adolescent Immunology CD34 Antigens CD34 Mice SCID Biology Biochemistry Mice Mice Inbred NOD Predictive Value of Tests Recurrence Proto-Oncogene Proteins hemic and lymphatic diseases medicine Animals Humans Stromal cell-derived factor 1 CXC chemokine receptors Aged Aged 80 and over Gene Expression Regulation Leukemic Chemotaxis Receptor Protein-Tyrosine Kinases Myeloid leukemia Cell Differentiation Adult Acute Myeloid Leukemia Cell Biology Hematology Middle Aged Prognosis Chemokine CXCL12 Haematopoiesis Phenotype medicine.anatomical_structure fms-Like Tyrosine Kinase 3 Leukemia Myeloid Acute Disease Cancer research biology.protein Female Stem cell Chemokines CXC Neoplasm Transplantation |
| Zdroj: | Blood, 104, 550-557. American Society of Hematology |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Recently it was shown that, analogous to normal hematopoietic cells, the level of CXC chemokine receptor 4 (CXCR-4) expression on acute myeloid leukemia (AML) cells correlates with stromal cell derived factor-1 alpha (SDF-1)-induced chemotaxis. As we speculated that an anomalous organ distribution of AML cells could affect cell survival and thus result in an altered fraction surviving chemotherapy, we examined a possible correlation between patient prognosis and CXCR-4 expression in AML patients. We found that patients with a high CXCR-4 expression in the CD34+ subset had a significantly reduced survival and a higher probability of relapse, resulting in a median relapse-free survival (RFS) of only 8.3 months. CXCR-4 expression was significantly higher in fetal liver tyrosine kinase-3 (Flt3)/internal tandem duplication (ITD) AML than in Flt3/wild-type (wt) AML. Covariate analysis indicated that the prognostic significance of Flt3/ITDs with respect to RFS was no more apparent when analyzed in conjunction with the expression of CXCR-4 in the CD34+ subset, suggesting that the poor prognosis of Flt3/ITD AML might be subordinate to the increased CXCR-4 expression. Using a granulocyte colony-stimulating factor receptor (G-CSF-R)-expressing 32D cell line, we observed that SDF-1/CXCR-4 interaction is required for the survival of myeloid differentiating cells, and it also induces a block in G-CSF-induced myeloid differentiation. These data suggest that the SDF-1/CXCR-4 axis may influence therapy responsiveness and defines unfavorable prognosis in AML. (Blood. 2004;104:550-557) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|