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  • Regarding the expression of NKp NCR Fig A and


    Regarding the expression of NKp46/NCR1 (Fig. 1A and B), both increased and decreased expression are observed depending on patients. Interestingly, the expression of the inducible molecule NKp44/NCR2 is clearly induced in 3 patients (PT1, PT2 and PT5) both regarding the percentage and the MFI. In contrast, we observed a decrease in the expression of NKp30/NCR3 in 3 patients (PT1, MK-571 sodium salt hydrate PT2 and PT7). Regarding NKG2D, a modification of expression was observed only in 2 patients, with 1 increase (PT4) and 1 increase (PT3) regarding the percentage of expression, while the MFI was decreased in most patients. Finally, we analyzed the expression of 2B4/CD244. This molecule is expressed in almost 100% of NK cells, and this percentage was not modified by 5-azacytidine treatment. In sharp contrast, when considering the MFI, we observed a drastic decrease from a mean MFI of 77±31 versus 36±15 (p<0.05). The low number of patient in our series precludes firm conclusions. Nonetheless, the 3-month treatment by the demethylating agent 5-azacitytine failed to restore or increase the expression of the NK activating molecules NCRs, NKG2D and 2B4/CD244, the expression of the later being on the contrary significantly down-regulated (decreased MFI in 6 out of 6 patients tested). Such a drastic down-regulation of 2B4/CD244 has also been observed in multiple myeloma but interestingly in this case only in bone marrow but not in peripheral blood [6]. We did not check NK MK-571 sodium salt hydrate phenotype in bone marrow of our RAEB patients since this analyze was not part of standard treatment follow-up. On the other hand, we failed to detect any increase in the inhibitory receptors we tested (CD158a, CD158b, CD158e, CD158i, CD159a, data not shown). Since the 2B4/CD244 is an important co-activating molecule for the NK, via its interaction with the EBV-inducible CD48 molecule, we can speculate that 5-azacytidine treatment could also contribute to immune deficiency via the inhibition of this co-activating pathway, although the rate of infection observed under 5-azacytidine did not increase in comparison with the other therapeutic options available for these patients [7] and was at least in part dependent on myelodysplasia characteristics, such as unfavorable cytogenetics [8]. In addition, these data could suggest Superrepressed the methylation status is probably not the central mechanisms for the NCRs and NKG2D transcriptional regulation, although the exact pattern of demethylation induced by 5-azacytidine is not entirely analyzed and cannot infer drug efficiency. Finally, our data also argue for the use of concomitant immune-stimulatory approaches such as lenalidomide [9] or other IMIDs class drugs in the treatment of RAEB or AML, in order to associate the supposed differentiation effects of demethylating agents with the development of an efficient anti-leukemic innate immune response.
    Authors contribution
    Acknowledgment This work was funded in part by the Association pour le DEveloppement de la REcherche Médicale (A.DE.RE.M).
    Introduction Acute appendicitis and typhlitis are the most common causes of gastrointestinal surgical complications in children undergoing chemotherapy for acute leukemia with reported incidences of 0.5–4.4% and 1.7–6.7% respectively [1–4]. Early diagnosis by radiologic imaging is essential as appendicitis usually requires emergent surgical management. Appendicitis with leukemic infiltration as the initial presenting feature may also rarely occur [5,6]. In such situations, the clinician must also balance the risk of further immunosuppression and chemotherapeutic toxicities with the risk of delaying appropriate leukemia therapy.
    Case series A retrospective case review of all children ≤18 years of age diagnosed with acute leukemia at our institution between January 2002 and December 2011 was performed after obtaining institutional IRB approval. Amongst 154 children eligible, three (1.9%) patients were diagnosed with appendicitis (Table 1). Appendicitis was diagnosed based on clinical, imaging and histologic findings.