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Blood, 15 July 2004, Vol. 104, No. 2, pp. 550-557.
Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2004-02-0566.
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Submitted February 17, 2004
Accepted March 17, 2004
Relation between CXCR-4 expression, Flt3 mutations and unfavourable prognosis of adult acute myeloid leukemia
Elwin J Rombouts*, Biljana Pavic, Bob Lowenberg, and Rob E Ploemacher
Hematology, ErasmusMC, Rotterdam, The Netherlands
* Corresponding author; email: w.rombouts{at}erasmusmc.nl.
Recently it was shown that, analogous to normal hematopoietic cells, the level of CXCR-4 expression on AML cells correlates with 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 RFS of only 8.3 months. CXCR-4 expression was significantly higher in Flt3/ITD AML than in Flt3/wt AML.Covariate analysis indicated that the prognostic significance of Flt3/ITDs with respect to RFS was no more apparent when analysed 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 G-CSF-R expressing 32D cell line we observed that SDF-1/CXCR4 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 unfavourable prognosis in AML.

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