Double minute chromosomes in acute myeloid leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia are associated with micronuclei, MYC or MLL amplification, and complex karyotype

Huh, Yang O.; Tang, Guilin; Talwalkar, Sameer S.; Khoury, Joseph D.; Ohanian, Maro; Bueso‐Ramos, Carlos E.; Abruzzo, Lynne V.

doi:10.1016/j.cancergen.2016.05.072

Cited by 44 publications

(48 citation statements)

References 38 publications

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“…Micronuclei are defined as small nuclear-like structures, and they usually contain amplified oncogenes or acentric chromosome fragments. It has recently been shown that micronuclei are closely correlated with oncogene amplification in the form of dmin in MDS/AML [Huh et al, 2016]. Interestingly, our results demonstrated that micronuclei could also be observed within leukemic blasts containing MYC amplification in ring chromosomes, even if these cells did not present dmin.…”

Section: Discussionsupporting

confidence: 60%

“…Storlazzi et al [2006] also showed a low expression of MYC but overexpression of TRIB1 by Northern blot analyses, suggesting that MYC is not the target gene of 8q24 amplifications. However, it was recently reported that MYC protein expression was observed in all cases of MDS/ AML with dmin [Huh et al, 2016]. We also demonstrated MYC protein overexpression at the diagnosis of AML and almost negative expression in hematological and cytogenetic CR.…”

Section: Discussionmentioning

confidence: 48%

“…As MYC gene amplification often results in increased MYC protein expression [Huh et al, 2016], we performed immunohistochemical staining on the bone marrow clot section for this protein. At the initial diagnosis of AML, about 80% of bone marrow cells were highly positive for MYC protein expression ( Fig.…”

Section: Case Report and Resultsmentioning

confidence: 99%

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

Yamamoto

Kawamoto²,

Kurata³

et al. 2017

Cytogenet Genome Res

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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.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 48%

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

Yamamoto

Kawamoto²,

Kurata³

et al. 2017

Cytogenet Genome Res

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“…They are often associated with complex karyotypes, and are generally associated with a poor prognosis. Dmins in myeloid neoplasms commonly harbor MYC or MLL gene amplification and manifest as micronuclei within leukemic cells [9,10].…”

Section: Discussionmentioning

confidence: 99%

“…46,XX [10] 47,XX,-5,-7,+20,add(20)(q11.2)x2,add(22)(q11.2),+2mar [2] 48,XX,-5,-7,+20,add(20)(q11.2)x2,add(22)(q11.2),+3mar [8] At the transformation to PEL The following example chromosome is representative of the karyotype: 55,XX,+2,+add(2)(q21),+6,add(7)(p22),+12,-13,add(14)(p11.2),+15,+16,+17,+19,+21,add(22)(p11.2),+mar,dmin 54,XX,+X,+6,-7,add(7)(p22),+8,add(10)(q22),+12,add(14)(p11.2),+15,+16,+17,+19,add(22) p11.2), +mar,dmin 54,XX,+2,-5,+6,add(7)(p22),+8,-9,+12,-13,add(14)(p11.2),+15,+19,+21,add(22)(p11.2),+4mar,dmin 100,XXXX,add(7)(p22)x2,+8,+8,-9,-9,-10,-11,+12,-13,-13,-13,add (14) [11][12][13]. In case of del(5q) MDS, a strong accumulation of p53 protein was found in erythroid progenitor cells; in contrast, myeloid or megakaryocyte lineage cells did not have increased p53 expression.…”

Section: Case 1 At the Diagnosis Of Mds-rcmdmentioning

confidence: 99%

Positive p53 immunostaining and erythroid maturation in two cases of pure erythroid leukemia with extremely complex karyotypes

Mita¹,

Akino²,

Shirato³

et al. 2016

Hematol Leuk

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Pure erythroid leukemia (PEL) is characterized as a neoplastic erythroid hyperproliferation with maturation arrest, showing highly complex karyotypes, prominent clonal evolution, and a very aggressive clinical course. Here, we describe two cases of PEL that evolved from myelodysplastic syndrome (MDS), focusing on the immunophenotypic, cytogenetic, and molecular features of these cases. Case 1: A 77-yearold woman was diagnosed with PEL that evolved from MDS-refractory cytopenia with multilineage dysplasia. Her disease progressed rapidly despite 5 cycles of azacitidine treatment. The bone marrow (BM) aspirate revealed hypercellular marrow with 92.4% erythroid cells, which expressed CD7 and CD36. Case 2: A 43-year-old woman had MDS-refractory anemia for more than 15 years. When her disease progressed rapidly, the BM aspirate revealed hypercellular marrow with 95.4% erythroid cells, which expressed CD235a. There were several significant findings in our cases. First, flow cytometric analysis of BM cells showed different stages of erythroid maturation. Second, cytogenetics revealed extremely complex karyotypes. Finally, immunohistochemistry showed strong nuclear staining for p53 in BM erythroid cells. We suggest that increased p53 protein expression is correlated with complex karyotypes and worse outcomes, indicating PEL with a high degree of malignant behavior.

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Optical genome mapping improves the accuracy of classification, risk stratification, and personalized treatment strategies for patients with acute myeloid leukemia

Loghavi,

Wei,

Ravandi

et al. 2024

American J Hematol

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Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision‐making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next‐generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four with failed karyotyping. The most common additional alterations identified by OGM included chromoanagenesis (n = 23), KMT2A partial tandem duplication (n = 11), rearrangements involving MECOM (n = 7), NUP98 (n = 2), KMT2A (n = 2), JAK2 (n = 2), and other gene fusions in 17 patients, with 10 showing novel fusion gene partners. OGM also pinpointed fusion genes in 17 (11%) patients where chromosomal rearrangements were concurrently detected by OGM and CBA. Overall, 24 (15%) aberrations were identified exclusively by OGM and had the potential to alter AML classification, risk stratification, and/or clinical trial eligibility. OGM emerges as a powerful tool for identifying fusion genes and detecting subtle or cryptic cytogenomic aberrations that may otherwise remain undetectable by CBA.

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Double minute chromosomes in acute myeloid leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia are associated with micronuclei, MYC or MLL amplification, and complex karyotype

Cited by 44 publications

References 38 publications

<b><i>MYC</i></b> Amplification in the Form of Ring Chromosomes 8 in Acute Myeloid Leukemia with t(11;16)(q13;p11.2)

<b><i>MYC</i></b> Amplification in the Form of Ring Chromosomes 8 in Acute Myeloid Leukemia with t(11;16)(q13;p11.2)

Positive p53 immunostaining and erythroid maturation in two cases of pure erythroid leukemia with extremely complex karyotypes

Optical genome mapping improves the accuracy of classification, risk stratification, and personalized treatment strategies for patients with acute myeloid leukemia

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