Spontaneous Splenic Rupture in Acute Myeloid Leukemia with Mixed-Lineage Leukemia Gene Rearrangement

2016 ◽  
Vol 01 (03) ◽  
Author(s):  
Gardner JA ◽  
Bao L ◽  
Ornstein DL
2021 ◽  
Vol 16 (11) ◽  
pp. 3406-3409
Author(s):  
Rita Tavarozzi ◽  
Tiziana Borra ◽  
Gioacchino Catania ◽  
Lorella Depaoli ◽  
Maria Teresa Corsetti ◽  
...  

2013 ◽  
Vol 55 (1) ◽  
pp. 209-212 ◽  
Author(s):  
Amer M. Zeidan ◽  
Mhairi Mitchell ◽  
Rina Khatri ◽  
Doha Itani ◽  
Sosipatros Boikos ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3546-3546
Author(s):  
Michael W.M. Kühn ◽  
Lars Bullinger ◽  
Jennifer Edelmann ◽  
Jan Krönke ◽  
Gröschel Stefan ◽  
...  

Abstract Abstract 3546 Rearrangements of the mixed lineage leukemia (MLL) gene are associated with the development of acute leukemia, and a variety of translocation partners have been described to date. In acute myeloid leukemia (AML), the translocation t(9;11)(p22;q23), resulting in the MLLT3-MLL fusion gene, is the most common genetic event involving MLL. The translocation t(9;11) can occur de novo, or as a consequence of previous chemotherapy (t-AML). Both types exhibit significant biological and clinical heterogeneity, and cooperating genetic events have been implicated underlying these heterogeneous phenotypes. To identify additional genomic abnormalities in AML with t(9;11), we performed high-resolution, genome-wide analysis of DNA copy number alterations (CNA) and copy neutral loss of heterozygosity (CN-LOH) using Affymetrix 6.0 single nucleotide polymorphism (SNP) microarrays in 34 AMLs with t(9;11) [de novo AML, n=22; t-AML, n=12]. Samples were also analyzed for AML-associated mutations: FLT3 [internal tandem duplication (ITD; 2/33); tyrosine kinase domain (TKD; 2/26)], NPM1 (0/28), CEBPA (0/23), IDH1 (0/28), IDH 2 (0/28), DNMT3A (0/19), NRAS (0/6); and deregulated expression of EVI1 (8/16). Control DNA from remission bone marrow or peripheral blood was available for paired analysis in 12 (33%) cases. Data were processed using reference alignment, dChipSNP, and circular binary segmentation. Paired analysis revealed a mean of 1.9 somatic CNAs per case (range: 0–12); 45% of cases lacked any CNAs. Deletions were more common than gains (1.73 losses/case vs. 0.25 gains/case; p =0.04). There were no significant differences in the mean number of CNAs between de novo and therapy-related cases (de novo AML: 1.0, range: 0–2; t-AML: 2.7, range: 0–12; p =0.93). Recurrent deletions were detected at chromosomal bands 7q36.1–36.2 (n=2) and at the chromosomal translocation breakpoint at 11q23 (n=2). The del(7q36.1–36.2) overlapped with a minimally deleted region at 7q36.1 that we previously identified in 8% of core-binding factor AML containing only 4 genes (PRKAG2, GALNT11, GALNTL5 and MLL3). The only gene contained in both regions was MLL3, a member of the mixed-lineage leukemia gene family. The most recurrent CNA was trisomy 8 (n=5), also detected by conventional cytogenetics in all 5 cases. Novel recurrent focal gains were identified at 9p22.1 (n=2; size: 341 Kb) and at 13q21.33-q22.1 (n=2; size: 1021 Kb) with each region containing genes potentially involved in cancer pathogenesis (ACER2 in 9p; KLF5 in 13q). Analysis of CN-LOH revealed no such lesion in any of the cases. In summary, our data provide a comprehensive survey of CNAs in a well characterized cohort of AMLs with t(9;11). These data demonstrate a very low occurrence of CNAs, with no significant differences between de novo and therapy-related cases and complete absence of CN-LOH. Interestingly, a number of novel recurrent secondary genetic alterations were identified. Determining the functional role of these lesions in leukemogenesis and drug resistance should provide new insights into t(9;11)-bearing AMLs. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
pp. 1-7
Author(s):  
Xiaohui Cai ◽  
Jinfei Wang ◽  
Jingtao Lu ◽  
Zhuxia Jia ◽  
Meiyu Chen ◽  
...  

Mixed lineage leukemia (<i>MLL) T10</i> is a relatively rare partner for the <i>KMT2A</i> lysine (K)-specific methyltransferase 2A gene. The common features and coexisting mutations of acute myeloid leukemia (AML) patients with <i>KMT2A-MLLT10</i> remain unknown. In this study, 10 adult AML patients with <i>KMT2A-MLLT10</i> fusions were picked up from 496 AML patients by using RT-polymerase chain reaction (PCR) and/or fluorescence in situ hybridization, and then screened for mutations in the 49 genes panel with next-generation sequencing and PCR, followed by direct Sanger sequencing. Of the 10 unique individuals identified, 6 were male and 4 were female (M:F ratio, 1.5:1) with ages ranging from 19 to 52 years (median 39.5 years). Most (90%, 9/10) patients with <i>KMT2A-MLLT10</i> were accompanied by additional mutations. Twelve mutated genes were detected, averaging 2.1 mutations per patient (range, 0–4). The most frequently mutated gene was <i>NRAS</i> (<i>n</i> = 5). Clinical and laboratory data pointed to common features: French American British-M5 subtype (<i>n</i> = 7), a high rate of relapse, and biomarkers CD33 (<i>n</i> = 10), CD117 (<i>n</i> = 9), CD13 (<i>n</i> = 8), and CD64 (<i>n</i> = 8). Overall, most patients harbored at least one mutation. A high incidence of mutations affecting the RAS signaling pathway or RAS regulating components was found in 50% (5/10) patients. The overall survival is about 12.0 months. Allogeneic-hematopoietic stem cell transplantation trends to improve survival in selected patients.


Blood ◽  
1989 ◽  
Vol 73 (3) ◽  
pp. 684-687 ◽  
Author(s):  
HH Gerhartz ◽  
CR Bartram ◽  
A Raghavachar ◽  
H Schmetzer ◽  
C Clemm ◽  
...  

Abstract Mononuclear cells from a 44-year-old patient with acute myeloid leukemia (AML) gave rise to a spontaneous permanent cell line cultured in suspension. The cell line was shown to be positive for Epstein-Barr virus nuclear antigen (EBNA). As expected, its composite phenotype was of B-cell type with B-cell antigens (CD 20, CD 21) and with monoclonal surface IgM of kappa type, but without detectable IgM secretion. Surprisingly, identical monoclonal rearrangements of the immunoglobulin heavy chain (JH) sequences could be demonstrated in the uncultured bone marrow AML cells and in the cell line that also had kappa light chain gene rearrangement. This is the first case to our knowledge of an EBNA positive B-cell line with identical monoclonal Ig heavy chain rearrangement as detected in myeloblastic leukemia cells.


Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6304-6314 ◽  
Author(s):  
Shunya Arai ◽  
Akihide Yoshimi ◽  
Munetake Shimabe ◽  
Motoshi Ichikawa ◽  
Masahiro Nakagawa ◽  
...  

Abstract Ecotropic viral integration site-1 (Evi-1) is a nuclear transcription factor that plays an essential role in the regulation of hematopoietic stem cells. Aberrant expression of Evi-1 has been reported in up to 10% of patients with acute myeloid leukemia and is a diagnostic marker that predicts a poor outcome. Although chromosomal rearrangement involving the Evi-1 gene is one of the major causes of Evi-1 activation, overexpression of Evi-1 is detected in a subgroup of acute myeloid leukemia patients without any chromosomal abnormalities, which indicates the presence of other mechanisms for Evi-1 activation. In this study, we found that Evi-1 is frequently up-regulated in bone marrow cells transformed by the mixed-lineage leukemia (MLL) chimeric genes MLL-ENL or MLL-AF9. Analysis of the Evi-1 gene promoter region revealed that MLL-ENL activates transcription of Evi-1. MLL-ENL–mediated up-regulation of Evi-1 occurs exclusively in the undifferentiated hematopoietic population, in which Evi-1 particularly contributes to the propagation of MLL-ENL–immortalized cells. Furthermore, gene-expression analysis of human acute myeloid leukemia cases demonstrated the stem cell–like gene-expression signature of MLL-rearranged leukemia with high levels of Evi-1. Our findings indicate that Evi-1 is one of the targets of MLL oncoproteins and is selectively activated in hematopoietic stem cell–derived MLL leukemic cells.


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