Identification and clinical evaluation of the receptor for hyaluronic acid-mediated motility [RHAMM/CD 168] in AML patients

RHAMM/CD 168 is a cell surface receptor for hyaluronan, a glycosaminoglycan that plays a fundamental role in cell growth, differentiation and motility. It is one of the leukemia-associated antigens [LAA] identified in patients with acute myeloid leukemia. In the present study, RHAMM expression was tested in the peripheral blood samples of 40 de novo AML patients as well as 15 healthy volunteers as a control group by RT-PCR. The mRNA of RHAMM was detected in 24/40 [60%] of the patients while it was not detected in the control group. There were no statistically significant difference between RHAMM positive and negative patients as regard their clinical and laboratory data, although the highest remission rate was achieved in RHAMM positive patients while RHAMM negative patients had a higher rate of adverse treatment outcome [relapse or death during induction chemotherapy. In conclusion, our findings are highly suggestive that the expression of RHAMM in newly diagnosed AML patients is a good prognostic marker as its expression is associated with facourable response to induction chemotherapy. Also being a tumour associated antigen, RHAMM represents a promising target for future immunotherapy

Expression of vascular endothelial growth factor and its receptors FLT-1 and KDR in acute leukemia: Clinical relevance and future prospects

Vascular endothelial growth factor [VEGF] and its receptors may play an important role in the pathophysiology of hematopoietic malignancies and the progression of leukemia. The present work aimed to study the expression of VEGF and its receptors namely FLT-1 [VEGFR-1] and KDR/FLK-1 [VEGFR-2] on the transcriptional level in fresh leukemic blast cells isolated from newly diagnosed AML and ALL patients by RT-PCR. The present study demonstrated that acute leukemia whether myeloblastic or lymphoblastic express VEGF and to less extent express its receptors namely FLT-1 and KDR. This may result in the generation of autocrine loop that may support leukemic cell survival and proliferation. On the contrary, to the lack of expression in normal bone marrow samples, VEGF, FLT-1 and KDR were expressed in considerable percentage of the studied AML and ALL patients. There was no significant relationship between the expression of VEGF or its receptors and patients' clinical or laboratory findings. Expression of VEGF and/or KDR receptors was associated with unfavorable treatment outcome and they were associated with risk of treatment failure. This data show that VEGF, FLT-1 and KDR may have clinical relevance and raise the possibility of using angiogenesis inhibitors as a novel therapeutic strategy in acute leukemia. By developing treatment strategies that target both the stromal and tumor compartments, drug resistance may be overcome, and the effect on therapeutic outcome enhanced