Double minute chromosomes in monoblastic (M5) and myeloblastic (M2) acute myeloid leukemia: Two case reports and a review of literature

Abstract

Double minutes (dmin) are small, paired chromatin bodies that lack a centromere and represent a form of extrachromosomal gene amplification. Although they have been found in a variety of solid tumors, their presence in hematological malignancies, especially acute myeloid leukemia (AML), is rare. In addition, the presence of dmin may be a mechanism for upregulated oncogene expression and is generally associated with a poor prognosis. We describe two patients who had dmin at initial presentation of AML, including the first case of M5a with C-MYC amplification on dmin, and another case with C-MYC amplification as the only cytogenetic finding. We review here a total of 33 cases with dmin in AML. C-MYC was amplified by the dmin in 25 cases, while other putative oncogenes were amplified in the other 8. Am.

Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461

“…Indeed, the first 14 of the 33 cases in the rare-aberrations group shown in Table 2 have chromosome aberrations that have been previously suggested to confer poor prognosis including t(6;9)(p23;q34) 9,32 ; t(9;22)(q34;q11.2) and complex variants 9,35,36 ; abnormalities of 3q, 9,10,37 ϩ4, 38,39 i(11)(q10), 39,40 and i(13)(q10) 39,[41][42][43] ; and double minutes (dmin). 44,45 While to our knowledge the prognostic relevance of abnormalities detected in the remaining 19 cases in this group has not yet been established, the survival of these patients was as poor as that of the aforementioned 14 patients (P ϭ .55; data not shown), suggesting that these aberrations may also confer a poor outcome, although no definitive conclusions can be drawn because of small patient numbers. A collaborative study pooling large datasets is required to investigate prognostic impact of each rare aberration separately.…”

Micronuclei‐associated MYC amplification in the form of double minute chromosomes in acute myeloid leukemia

“…Double minute chromosomes (dmin) are small chromatin bodies that lack centromeres and frequently mediate oncogene amplification in human tumors, although they are rarely found in AML. These chromosomes are commonly correlated with amplification of MYC at 8q24 or less commonly MLL at 11q23 [3][4][5]. The presence of dmin as part of complex karyotypes in AML appears to bring about chemotherapy resistance and rapid progression of the disease.…”

A mechanism of palindromic gene amplification in Saccharomyces cerevisiae

“…Gene amplification is also associated with abnormal processes, such as increased drug resistance (Schimke et al 1978;Paquin et al 1992) and the onset and progression of tumorigenesis (Lengauer et al 1998). Several mechanisms of gene amplification have been described, including the formation and overreplication of extrachromosomal circular elements (Thomas et al 2004), in situ endoreplication (Botchan and Levine 2004), unequal sister chromatid exchange (Axelrod et al 1994), and palindromic amplification.…”