Patients with t(8;21) and EML have a low CR rate and overall survival. An aggressive local and systemic induction therapy should be considered for this patient subset. The effectiveness of HDAC intensification in t(8;21) patients with EML is uncertain and warrants further study.

These data demonstrate that failure-free survival and overall survival of patients with t(8;21)(q22;q22) may be compromised by treatment approaches that do not include sequential high-dose cytarabine therapy.

The p53 tumor suppressor is activated in response to a variety of cellular stress signals, including DNA damage. Its ability to facilitate growth arrest and/or cell death in response to such signals is believed to be the basis for its tumor suppressor function (see references 5, 16, 22, and 27 for reviews). However, specific in vivo signals that trigger tumor suppression have not been identified. Sixty to eighty percent of the spontaneous malignancies in p53-deficient mice are thymic lymphomas (13, 17), indicating that natural thymocyte events signal p53 tumor suppression. The favored hypothesis is that flawed T-cell receptor (TCR) gene recombination events signal p53-dependent elimination of damaged cells (15,17,24,28). p53 inactivation would thus facilitate the survival of cells carrying tumorigenic mutations. This hypothesis is consistent with several observations, including that (i) double-strand DNA breaks (DSBs) trigger p53 responses (29), (ii) p53 is required for DNA damage-induced thymocyte apoptosis (11, 23), (iii) thymic lymphomas induced by p53 deficiency are clonal, indicating that additional tumorigenic events are required (38), and (iv) in scid mice, which accumulate V(D)J breaks, lymphoid malignancies are accelerated by p53 deficiency (15, 28). Since V(D)J translocations are frequently associated with oncogene activation in human and mouse lymphoid tumors, it is reasonable to suspect that these events may be involved in tumorigenesis in the absence of p53-mediated surveillance.V(D)J recombination affects TCR and immunoglobulin (Ig) DNA rearrangement in developing T and B cells to generate a variety of antigen receptor specificities. Normally this process occurs during specific stages of T-and B-cell differentiation to yield a single productive rearrangement per cell for each polypeptide component of the receptor. The initiating event in V(D)J recombination, the generation of specific DSBs, requires two recombination activating genes (RAGs), RAG-1 and RAG-2 (9, 31). Mice deficient in either of these genes fail to undergo V(D)J recombination and are immunodeficient due to the lack of mature T and B cells (25,37). Thus, these mice provide an approach for assessing the role of V(D)J recombination in thymomagenesis associated with p53 deficiency. Here we examine the impact of inactivating V(D)J recombination on tumorigenesis by introducing RAG deficiencies and/or rearranged TCR transgenes into mice with a thymocyte p53 deficiency. Additionally, we analyze the chromosomes of p53-deficient thymomas for evidence of TCR translocations and other aberrations. MATERIALS AND METHODSMice. RAG-1 Ϫ/Ϫ (C57BL/6J-sv/129), scid/scid (C57BL/6J), TgN(TcrLCMV) (B6D2), and p53 Ϫ/Ϫ (C57BL/6J) mice were from Jackson Laboratory, and RAG-2 Ϫ/Ϫ mice (129, SvEv) were from Taconic Laboratory. TgT⌬N mice (B6D2), previously referred to as TgLST1135, abundantly express the dl1135 simian virus 40 (SV40) large T antigen (T-Ag) in thymocytes under the regulation of the lymphotropic papovavirus transcriptional signals (38). Although l...

Abstract. The Cancer and Leukemia Group B has performed central review of karyotypes submitted by institutional cytogenetics laboratories from patients with acute myeloid (AML) and acute lymphoblastic (ALL) leukemia since 1986. We assessed the role of central karyotype review in maintaining accurate, high quality cytogenetic data for clinical and translational studies using two criteria: the proportion of karyotypes rejected (i.e. inadequate), and, among accepted (i.e. adequate) cases, the proportion of karyotypes whose interpretation was changed on central karyotype review. We compared the first four years during which central karyotype review was performed with a recent 4-year period and found that the proportion of rejected samples decreased significantly for both AML and ALL. However, during the latter period, central karyotype reviews still found 8% of AML and 16% of ALL karyotypes inadequate. Among adequate cases, the karyotype was revised in 26% of both AML and ALL samples. Some revisions resulted in changing the patients' assignment to particular World Health Organization diagnostic categories and/or moving patients from one prognostic group to another. Overall, when both data on rejection rates and data on karyotype revisions made in accepted cases were considered together, 32% of AML and 38% of ALL samples submitted were either rejected or revised on central karyotype review during the recent 4-year period. These data underscore the necessity of continued central karyotype review in multiinstitutional cooperative group studies.

No abstract

No abstract

Chromosomal banding data on three species of Tatera from Kenya significantly alter the previous hypothesis of relationships between and within the genera Tatera and Gerbillurus based on cladistic analyses and the rule of parsimony (Qumsiyeh, 1986b). Of the many possible hypothetical relationships, the most parsimonious tree showed three homoplasies and allowed the genus Gerbillurus to be paraphyletic. The alternative trees, depicting larger number of homoplasies but with homoplasies restricted to fusion or fission events, were compatible with the morphological data in supporting the monophyly of Gerbillurus. To choose between the hypothesis based on the most parsimonious chromosomal tree and those supported by both morphology and slightly less parsimonious chromosomal trees, we performed an electrophoretic study on this group of gerbils. The conclusions are that the genus Gerbillurus is monophyletic and represents a branch that is closely related to the T. robusta group of Taterillini. The study documents that fissions and fusions must have occurred frequently and that in some cases the same fusions were acquired in two independent lineages in numbers exceeding those that are predicted by strict parsimony. The results raise questions about the validity of systematic conclusions based solely on fusion/fission data and utilizing the parsimony criterion.

No abstract