SummaryActivating mutations of the FMS-like tyrosine kinase 3 gene (FLT3) occur in approximately one-third of patients with acute myeloid leukaemia (AML) and predict for a poor outcome. Heat shock protein 90 (Hsp90) is a molecular chaperone that is frequently used by cancer cells to stabilise mutant oncoproteins. Mutant FLT3 is chaperoned by Hsp90 in primary AML blasts whereas unmutated FLT3 is not, making Hsp90 inhibitors potentially useful therapeutically. The present study showed that inhibition of Hsp90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) was cytotoxic to primary AML cells expressing mutant FLT3. Inhibition of Hsp90 results in altered downstream signalling effects in primary AML cells with disruption of Janus kinase-signal transducer and activator of transcription (JAK-STAT), mitogen-activated protein kinase and phosphatidylinositol 3/AKT signalling pathways. Co-treatment of blasts with 17-AAG and cytarabine resulted in a synergistic or additive effect in approximately 50% of AML cases tested. Our results confirm that Hsp90 is a valid molecular target in the therapy of AML. Inhibition of Hsp90 in parallel with conventional AML therapies may have particular benefit in those patients with the poor prognostic FLT3 mutant disease.Keywords: acute myeloid leukaemia, FLT3, heat shock protein 90, Ara-C, 17-allylamino-17-demethoxygeldanamycin. research paper ª

Incidence rates and estimated residual risk indicate that the current risk of TTVIs attributable to blood donation is relatively low in the UAE. The study recommends the parallel use of both serology and ID-NAT TTVIs screening in blood donations and suggests the exclusion of antibody to hepatitis B core antigen-positive donations as this can eliminate the potential infectivity of these units with marginal effects on the blood stock in UAE.

BackgroundTo ensure an adequate and safe blood supply, it is crucial to select suitable donors according to stringent eligibility criteria. Understanding the reasons for donor deferral can help in planning more efficient recruitment strategies and evaluating donor selection criteria. This study aims to define donor pre-donation deferral rates, causes of deferral, and characteristics of deferred donors in Dubai.Materials and methodsThis retrospective study was conducted on all donors who presented for allogeneic blood donation between January 1, 2010, until June 30, 2013, in Dubai Blood Donation Centre, accredited by the American Association of Blood Banks. The donation and deferral data were analyzed to determine the demographic characteristics of accepted and deferred donors, and frequency analyses were also conducted.ResultsAmong 142,431 individuals presenting during the study period, 114,827 (80.6%) were accepted for donation, and 27,604 (19.4%) were deferred. The overall proportion of deferrals was higher among individuals less than 21 years old (35%, P<0.000), females (44% were deferred compared to 15% of males, P<0.0001), and first-time donors (22% were deferred vs 14% of repeat donors, P<0.0001). The main causes for a temporary deferral were low hemoglobin and high blood pressure.DiscussionThe deferral rate among blood donors in Dubai is relatively high compared to the internationally reported rates. This rate was higher among first-time donors and females, with low hemoglobin as the major factor leading to a temporary deferral of donors. Strategies to mitigate deferral and improve blood donor retention are urged in Dubai to avoid additional stress on the blood supply.