Summary. The Wiskott-Aldrich syndrome (WAS) is an Xlinked recessive disorder characterized by thrombocytopenia, immunode®ciency and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this study we investigated the role of WASP in the differentiation of CD34-positive (CD34 ) cells isolated from the bone marrow of patients with WAS (n 5) or with XLT (n 4). Megakaryocyte colony formation was signi®cantly decreased in patients with WAS when compared with normal controls. The formation of granulocyte-macrophage colonies and erythroid bursts were also decreased in WAS patinets. In contrast, in XLT patients, formation of all these colonies was normal. However, in vitro proplatelet formation of megakaryocytes induced by thrombopoietin was markedly decreased in both XLT and WAS. Electron microscopic examination revealed that megakaryocytes obtained from WAS or XLT patients grown in vitro had abnormal morphologic features, which seemed to be caused by defective actin cytoskeletal organization, including labyrinth-like structures of the demarcation membrane system and deviated distribution of the a-granules and demarcation membrane system. These observations indicate that WASP is involved in the proliferation and differentiation of CD34 haemopoietic progenitor cells probably by its participation in signal transduction and in the regulation of the cytoskeleton.

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This study analyzed data on 35 infants with acute myeloid leukemia (AML) who were treated with intensive chemotherapy between 1995 and 1998 in Japan. The incidence of boys, younger age (< 6 months old), and hyperleukocytosis at onset was high in patients with the M4/M5 subtype (n ‫؍‬ 23) in the French-AmericanBritish classification, compared with the non-M4/M5 subtype (n ‫؍‬ 12). Thirteen (56%) and 16 (70%) patients with the M4/M5 subtype also showed 11q23 translocations and MLL gene rearrangements, respectively, whereas only one patient with the non-M4/M5 subtype had this rearrangement. All 35 patients were treated with the ANLL91 protocol consisting of etoposide, high-dose cytarabine, and anthracyclines. Overall survival and the event-free survival (EFS) rates at 3 years of all patients were 76% (95% confidence interval [CI], 61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no significant difference between 2 subgroups divided by age, gender, presence of the MLL gene rearrangements, and white blood cell count at onset; EFS in patients with the M4/M5 subtype tended to be better than those with the non-M4/M5 subtype. Although all 6 patients who underwent allogeneic stem cell transplantation (SCT) have been in complete remission, no benefit of SCT was confirmed. These findings suggest that the intensive chemotherapy with the ANLL91 protocol might have been responsible for the observed good outcome of infant AML, even without SCT. The presence of the MLL gene rearrangements or the age at onset had no impact on the outcome of infant AML. IntroductionInfants with acute myeloid leukemia (AML) generally show monoblastic or myelomonoblastic features with hyperleukocytosis, extramedullary involvement, and MLL gene rearrangements by cytogenetic analysis. 1,2 The outcome and prognostic factors in infants with AML remain generally obscure. Several studies have reported that the presence of MLL gene rearrangements was of prognostic significance, in addition to the high white blood cell (WBC) count at diagnosis in both adults and infants with AML. 3,4 Pui and coworkers 5 reported that male gender and a WBC count of more than 50 000/L were significantly associated with an inferior outcome in infant AML. Molecular abnormalities of 11q23 translocations or MLL gene rearrangements in infant AML have been correlated with an M4 or M5 subtype in the French-AmericanBritish (FAB) classification and hyperleukocytosis. 1,2,[4][5][6] The event-free survival (EFS) of infants with AML treated with chemotherapy has been reported to be 32% to 34%. 7,8 However, the presence of MLL gene rearrangements failed to correlate with treatment response, 5,6 in contrast to the extremely poor outcome of infants with acute lymphoblastic leukemia (ALL) with the rearrangements. [9][10][11] The clinical outcomes of infant AML with MLL gene rearrangements were also similar to those of childhood AML. 6 The reason for this apparent discrepancy in the treatment outcome between patients with ALL and AML is not clear. Moreover, indications of...

Delay of the initial lumbar puncture and intrathecal injection of chemotherapy seems to be feasible in children with ALL. Further controlled evaluations are needed to establish the validity of this conclusion.