scholarly journals Ring Chromosome 8 as a sole abnormality: An adverse prognostic indicator in Acute Myeloid Leukemia?

2018 ◽  
Author(s):  
Vishal Ashok ◽  
Satish Kumar ◽  
Jayarama S Kandandale ◽  
Tambarahalli S Sundareshan
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Ring Chromosome ◽  
Prognostic Indicator ◽  
Chromosome 8 ◽  
Acute Myeloid

scholarly journals MYC Amplification in the Form of Ring Chromosomes 8 in Acute Myeloid Leukemia with t(11;16)(q13;p11.2)

2017 ◽  
Vol 153 (3) ◽  
pp. 131-137 ◽  
Author(s):  
Katsuya Yamamoto ◽  
Shinichiro Kawamoto ◽  
Keiji Kurata ◽  
Akihito Kitao ◽  
Yu Mizutani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Ring Chromosome ◽  
Chromosome 8 ◽  
Small Ring ◽  
Ring Chromosomes ◽  
Multiple Copies ◽  
Recurrent Translocation ◽  
Acute Myeloid

Oncogene amplification is uncommon in acute myeloid leukemia (AML). Cytogenetically, it is primarily found as double minute chromosomes (dmin) or homogeneously staining regions (hsr). A 62-year-old woman was admitted to our hospital because of anemia and thrombocytopenia. Her bone marrow was hypercellular with 78.6% myeloperoxidase- positive blasts. Some had micronuclei. The patient was diagnosed with AML M2 and remains in complete remission (CR) after induction therapy. G-banding at diagnosis showed 51,XX,t(11;16)(q13;p11.2),+r1,+mar1×4. Spectral karyotyping confirmed t(11;16) and revealed that the ring and the marker chromosomes were derived from multiple copies of ring chromosome 8. Fluorescence in situ hybridization (FISH) with a MYC probe at 8q24 detected amplified MYC signals on 1 large and 4 small ring chromosomes 8. One MYC signal was deleted from one of the 2 chromosomes 8. FISH with a FUS probe at 16p11.2 showed monoallelic deletion of FUS. Immunohistochemistry demonstrated MYC protein overexpression at diagnosis and almost negative expression in CR. These results indicate that MYC amplification could occur in ring chromosomes without dmin. A cryptic MYC deletion suggests that an episome model could be applicable to MYC amplification in ring chromosomes as observed for dmin and hsr. Furthermore, considering 2 further reported cases, t(11;16)(q13;p11) may be a very rare but recurrent translocation in AML.

scholarly journals Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ting-juan Zhang ◽  
Zi-jun Xu ◽  
Yu Gu ◽  
Ji-chun Ma ◽  
Xiang-mei Wen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Related Gene ◽  
Targeted Bisulfite Sequencing ◽  
Specific Pcr ◽  
Frequent Event ◽  
Acute Myeloid

Abstract Background Obesity confers enhanced risk for multiple diseases including cancer. The DNA methylation alterations in obesity-related genes have been implicated in several human solid tumors. However, the underlying role and clinical implication of DNA methylation of obesity-related genes in acute myeloid leukemia (AML) has yet to be elucidated. Results In the discovery stage, we identified that DNA methylation-associated LEP expression was correlated with prognosis among obesity-related genes from the databases of The Cancer Genome Atlas. In the validation stage, we verified that LEP hypermethylation was a frequent event in AML by both targeted bisulfite sequencing and real-time quantitative methylation-specific PCR. Moreover, LEP hypermethylation, correlated with reduced LEP expression, was found to be associated with higher bone marrow blasts, lower platelets, and lower complete remission (CR) rate in AML. Importantly, survival analysis showed that LEP hypermethylation was significantly associated with shorter overall survival (OS) in AML. Moreover, multivariate analysis disclosed that LEP hypermethylation was an independent risk factor affecting CR and OS among non-M3 AML. By clinical and bioinformatics analysis, LEP may be also regulated by miR-517a/b expression in AML. Conclusions Our findings indicated that the obesity-related gene LEP methylation is associated with LEP inactivation, and acts as an independent prognostic predictor in AML.

scholarly journals Tritsomy 8 Acute Myeloid Leukemia Analysis Reveals New Insights of DNA Methylome with Identification of HHEX as Potential Diagnostic Marker

2015 ◽  
Vol 7 ◽  
pp. BIC.S19614 ◽  
Author(s):  
Marwa H. Saied ◽  
Jacek Marzec ◽  
Sabah Khalid ◽  
Paul Smith ◽  
Gael Molloy ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Diagnostic Marker ◽  
Cpg Island ◽  
Global Analysis ◽  
Extra Chromosome ◽  
Chromosome 8 ◽  
Trisomy 8 ◽  
Acute Myeloid

Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI ( P = 7.88 · 10–11identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML.

scholarly journals Translocation breakpoints are clustered on both chromosome 8 and chromosome 21 in the t(8;21) of acute myeloid leukemia

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 592-596 ◽  
Author(s):  
JE Tighe ◽  
A Daga ◽  
F Calabi
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chromosome 8 ◽  
Chromosome 21 ◽  
Novel Gene ◽  
Translocation Breakpoints ◽  
Acute Myeloid

Abstract The t(8;21)(q22;q22) is consistently associated with acute myeloid leukemia (AML) M2. Recent data have suggested that breakpoints on chromosome 21 are clustered within a single intron of a novel gene, AML1, just downstream of a region of homology to the runt gene of D melanogaster. In this report, we confirm rearrangement at the same location in at least 12 of 18 patients with t(8;21). Furthermore, we have isolated recombinant clones spanning the breakpoint regions on both the der(8) and the der(21) from one patient. By using a chromosome 8 probe derived from these clones, we show that t(8;21) breakpoints are also clustered on chromosome 8.

RUNX1/AML1 DNA Binding Domain and ETO/MTG8 NHR2 Dimerization Domain Are Critical to AML1−ETO9a Leukemogenesis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 772-772
Author(s):  
Ming Yan ◽  
Scott Hiebert ◽  
Dong-Er Zhang
Keyword(s):  
Acute Myeloid Leukemia ◽  
Dna Binding ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
Binding Domain ◽  
Chromosome 8 ◽  
Chromosome 21 ◽  
Dna Binding Domain ◽  
Dimerization Domain ◽  
Acute Myeloid

Abstract The 8;21 translocation, which involves the gene encoding the RUNX family DNA binding transcription factor AML1 (RUNX1) on chromosome 21 and the ETO (MTG8) gene on chromosome 8, generates AML1−ETO fusion proteins. Previous analyses have demonstrated that full length AML1−ETO blocks AML1 function and requires additional mutagenic events to promote leukemia in mice. More recently, we have identified an alternatively spliced form of AML1−ETO, AML1−ETO9a, from t(8;21) AML patient samples (Yan et al. Nat. Med.12:945–949, 2006). AML1−ETO9a lacks the C−terminal NHR3 and NHR4 domains of AML1−ETO and is highly leukemogenic in mice. Here, we report that the AML1 DNA binding domain and the ETO NHR2 dimerization domain, but not the ETO NHR1 domain are critical for the induction of acute myeloid leukemia by AML1−ETO9a. Using retroviral mediated gene expression and hematopoietic cell transplantation in recipient mice, we examined AML1−ETO9a, AML1−ETO9a without the NHR1 domain [AML1−ETO9a (dNHR1)] or the NHR2 domain [AML1−ETO9a(dNHR2)], without a histone deacetylase/Sin3A interacting domain between NHR1 and NHR2 [AML1−ETO9a(d350–428)], and mutant AML1−ETO9a proteins that have lost the capacity to bind DNA [AML1−ETO9a(L148D)] and [AML1−ETO9a(R173Q)] in leukemogenesis. All of the mice transplanted with AML1−ETO9a (n =11) and AML1−ETO9a(dNHR1) (n = 12) expressing cells developed acute myeloid leukemia with a similar phenotype (Lin−/c−kit+) within 21 weeks. The median survival times of mice with AML1−ETO9a and AML1−ETO9a(dNHR1) are 9.4 weeks and 10.5 weeks, respectively. Furthermore, all of the mice expressing AML1−ETO9a(d350–428) (n = 11) also developed leukemia with a median survival time of 17.2 weeks. Significant numbers of AML1−ETO9a(d350–428) expressing cells are positive for myeloid markers CD11b and Gr1 in these leukemic mice. In contrast, none of the mice with AML1−ETO9a(dNHR2) (n = 14), AML1−ETO9a(L148D) (n = 8), and AML1−ETO9a(R173Q) (n = 8) expressing hematopoietic cells developed leukemia. Taken together, these data suggest that the AML1 DNA binding domain and the ETO NHR2 domain are required for AML1−ETO9a induced leukemia development and the region between amino acids 350 and 428 of AML1−ETO9a also affects the differentiation stage and latency of leukemogenesis.

Tetrasomy of Chromosome 8 In A Patient with Acute Myeloid Leukemia

1995 ◽  
Vol 19 (3-4) ◽  
pp. 355-358 ◽  
Author(s):  
Gavin M. Cull ◽  
Densie J. Howe ◽  
Michael Stack-Dunne ◽  
Malcolm J. Phillips ◽  
Stephen A. Johnson
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chromosome 8 ◽  
Acute Myeloid

scholarly journals Ring chromosome 11 with KMT2A (MLL; 11q23) amplification and deletion in a patient with acute myeloid leukemia

2017 ◽  
Vol 5 (1) ◽  
pp. 3
Author(s):  
Stephanie Liu ◽  
Tahmeena Ahmed ◽  
Yupo Ma ◽  
Rajarsi Gupta ◽  
Theresa Mercado ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Ring Chromosome ◽  
Chromosome 11 ◽  
Acute Myeloid
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