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 De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ismael F. Alarbeed ◽  
Abdulsamad Wafa ◽  
Faten Moassass ◽  
Bassel Al-Halabi ◽  
Walid Al-Achkar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Type A ◽  
Chemotherapeutic Treatment ◽  
Acute Myeloid ◽  
New Mutations

Abstract Background Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. Case presentation Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. Conclusions To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.

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 DNA damage in acute myeloid leukemia patients of Northern Mexico

2017 ◽  
Author(s):  
Martha I. Dávila-Rodríguez ◽  
Elva I. Cortés-Gutiérrez ◽  
Roberto Hernández-Valdés ◽  
Karla Guzmán-Cortés ◽  
Rosa E. De León-Cantú ◽  
...  
Keyword(s):  
Dna Damage ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fluorescent In Situ Hybridization ◽  
Control Group ◽  
Repair Pathway ◽  
Blood Leukocytes ◽  
Northern Mexico ◽  
Acute Myeloid

The purpose of this study was to evaluate DNA damage in the whole genome of peripheral blood leukocytes from patients with acute myeloid leukemia (AML) compared with a control group using DNA breakage detection-fluorescent in situ hybridization (DBD-FISH). Our results suggest that the DNA damage detected in patients with newly diagnosed AML was similar to that observed for the controls; this might be explained by the stimulation of a repair pathway by the pathogenesis itself. These findings indicate that inhibiting the repair pathway could be proposed to enhance the efficacy of chemotherapy.

scholarly journals Early Fluorescence in situ Hybridization Assessment during Acute Myeloid Leukemia Induction Chemotherapy

2018 ◽  
Vol 139 (3) ◽  
pp. 171-175
Author(s):  
Robert Schneidewend ◽  
Paul Hosking ◽  
Ruta Brazauskas ◽  
Jess Peterson ◽  
Carlie Beaudin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Atypical Phenotype and Treatment Response Pattern in a Patient with FIP1L1-PDGFRα Mutation

2018 ◽  
Vol 140 (2) ◽  
pp. 67-70 ◽  
Author(s):  
Mihir Bikhchandani ◽  
Ryan Johnson ◽  
Bertrand Tuan ◽  
Ayalew Tefferi
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasm ◽  
Myeloproliferative Disorders ◽  
Second Line ◽  
Imatinib Resistance ◽  
Hypercellular Marrow ◽  
Atypical Phenotype ◽  
Acute Myeloid

Myeloproliferative disorders with eosinophilia may possess the FIP1L1-PDGFRα gene rearrangement. When this rearrangement is present, imatinib usually results in complete remission. In rare cases of imatinib resistance, there is poor evidence guiding second-line therapy. We present the case of a 71-year-old male who presented with abdominal discomfort, fevers, and leukocytosis with eosinophilia. The patient was diagnosed with a myeloproliferative neoplasm with eosinophilia and FIP1L1-PDGFRα rearrangement after a bone marrow evaluation revealed hypercellular marrow with eosinophilia and fluorescence in situ hybridization identified the FIP1L1-PDGFRα rearrangement. The patient was successfully treated with imatinib. Within months he relapsed and converted into acute myeloid leukemia. The patient was then treated with ponatinib which induced and maintained clinical and hematological remission for 2 months. That ponatinib briefly induced remission in our patient with acute myeloid leukemia arising from a myeloproliferative neoplasm with eosinophilia and FIP1L1-PDGFRα fusion may merit exploration of ponatinib as a potential second-line treatment option for this patient population. This is especially true given the lack of reliable therapies in instances of imatinib resistance.

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