Aggressive natural killer cell leukemia: clinical features and treatment outcome.

of viable CD41+ cells be harvested at day 14 of culture. Bcl-xL mRNA was detected at high levels in all samples of RAEB CD34+ cells at day 0, and it appeared progressively down-regulated at days 7 and 14 of culture (Figure 2A). Moreover, the Bcl-xL expression pattern was similar in control cultures and in cultures containing anti-TGF-β1 neutralizing antibody (Figure 2B). The deregulated expression of Bcl-xL in MDS CD34+ cells was not dependent on impaired TGF-β1 autocrine production. In fact, we have previously demonstrated that MDS CD34+ cells induced towards megakaryocytic differentiation produce TGF-β1.1 In conclusion, our data confirm that Bcl-xL up-regulation plays a fundamental role in normal megakaryocytopoiesis and demonstrate that it depends on the autocrine TGF-β1 produced by differentiating cells. Furthermore, this study highlights that Bcl-xL expression in RAEB CD34+ cells undergoing megakaryocytic commitment is completely altered and suggests that it can play a role in their defective differentiation capacity. Maurizio Martini,#* Myriam Luongo,#° Luciana Teofili,° Antonella Di Mario,° Giuseppe Leone,* Luigi Maria Larocca* Istituti di*Anatomia Patologica ed °Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy #These authors equally contributed to this work. Funding: This study was supported in part by Grants ex-60% from Ministero dell’Università e della Ricerca, Rome, Italy. Correspondence: Maurizio Martini, M.D., Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, largo Francesco Vito n°1, 00168, Rome, Italy. Phone: international +39.06.30154270. Fax: international +39.06.30155883. E-mail: [email protected]