Characterization of acute myeloid leukemia with MLL rearrangements – no increase in the incidence of coexpression of lymphoid-associated antigens on leukemic blasts

Tien, Hwei‐Fang; Hsiao, Ching Hua; Tang, Jih‐Luh; Tsay, Woei; Hu, C. K.; Kuo, Yueh‐Hsiung; Wang, C H; Chen, Y C; Shen, Ming‐Ching; Lin, Dong; Lin, Kai Hsin

doi:10.1038/sj.leu.2401791

Cited by 13 publications

(11 citation statements)

References 27 publications

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“…17,18,27 Although infant AML was found to have a high frequency (around 50%) of the MLL gene rearrangement, they usually involved reciprocal translocation of the MLL gene with its partner genes. 8,12,16,28 Little is known about the frequency of partial tandem duplication of the MLL gene in infant as well as in other pediatric AML. In this study, we did not observe such abnormality in any infant, but children older than 1 year tended to have a higher frequency of MLL duplication than patients in other age groups, especially among the patients with normal karyotype.…”

Section: Discussionmentioning

confidence: 99%

“…12 Genomic DNAs were digested with restriction enzymes BamHI and HindIII. After being size-fractionated by electrophoresis and transferred to Hybond membrane Leukemia (Amersham Pharmacia Biotech, Amersham, UK), they were hybridized with 32 P-dCTP-labelled probe.…”

Section: Detection Of Partial Tandem Duplication Of the Mll Genementioning

confidence: 99%

“…5,6 Rearrangements of the MLL gene can be demonstrated not only in most acute leukemias with various 11q23 translocations [7][8][9] but also in some acute myeloid leukemia (AML) without cytogenetic abnormalities at 11q23. [10][11][12] gene in the latter condition has revealed that the gene is rearranged by partial tandem duplication. 13 The duplication involves a portion of the gene corresponding to the aminoterminus of the MLL protein which contains the AT hook and a region of homology to DNA methyltransferase (MT) motifs, two domains suggested to be critical for leukemogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23

Kuo

Tang

et al. 2002

Leukemia

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The clinical and biological features of acute myeloid leukemia (AML) with 11q23/MLL translocations are well known, but the characteristics of AML with partial tandem duplication of the MLL gene have not been explored comprehensively. In this study, MLL duplication was analyzed, in 81 AML patients without chromosomal abnormalities at 11q23, using Southern blotting, genomic DNA polymerase chain reaction (PCR), reversetranscription PCR and complementary DNA sequencing. Nine patients showed partial tandem duplication of the MLL gene, including eight (12%) of the 68 with normal karyotype. Seven patients showed fusion of exon 6/exon 2 (e6/e2), one, combination of differentially spliced transcripts e7/e2 and e6/e2, and the remaining one, combination of e8/e2 and e7/e2. Among the patients with normal karyotype, children aged 1 to 15 showed a trend to higher frequency of MLL duplication than other patients (2/5 or 40% vs 6/62 or 10%, P = 0.102). The patients with tandem duplication of the MLL gene had a significantly higher incidence of CD11b expression on leukemic cells than did those without in the subgroup of patients with normal karyotype (75% vs 28%, P = 0.017). There were no significant differences in the expression of lymphoid antigens or other myeloid antigens between the two groups of patients. In adults, the patients with MLL duplication had a shorter median survival time than those without (4.5 months vs 12 months, P = 0.036). In conclusion, partial tandem duplication of the MLL gene is associated with increased expression of CD11b on leukemic blasts and implicates poor prognosis in adult AML patients. The higher frequency of MLL duplication in children older than 1 year, than in other age groups, needs to be confirmed by further studies.

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Section: Discussionmentioning

confidence: 99%

Section: Detection Of Partial Tandem Duplication Of the Mll Genementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23

Kuo

Tang

et al. 2002

Leukemia

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“…[212][213][214] Relatively frequent expression of B cell markers has been reported 170 but other studies have not confirmed this finding. 213,215 Most cases of AML with 11q23 alterations aberrantly express NG2 homologue, similarly to the ALL cases with MLL rearrangements (see section ALL with rearrangements of MLL for details on NG2). 6 AML t(9;11) in children is also associated with M5 FAB category and strong expression of NG2, HLA-DR, CD33, CD65w and CD4, while CD13, CD14 and CD34 are low.…”

Section: Abnormalities Of Mll Genementioning

confidence: 99%

Antigen expression patterns reflecting genotype of acute leukemias

2002

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“…[13][14][15] A number of studies have characterized the immunophenotype of AML with 11q23 chromosomal translocations. [16][17][18] However, the immunophenotype characteristics of the PTD of MLL gene have only been described in one report. 19 Another application of FC is the study of minimal residual disease (MRD) in these patients.…”

Section: Introductionmentioning

confidence: 99%

Acute myeloid leukemia with MLL rearrangements: clinicobiological features, prognostic impact and value of flow cytometry in the detection of residual leukemic cells

Muñoz

Villamor³

et al. 2003

Leukemia

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The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangements that occur in a variety of hematological malignancies. MLL rearrangements are associated with distinct clinical features and a poor prognosis. The aim of this study was to analyze the incidence and the prognostic significance of MLL rearrangements in a consecutive series of adult AML patients and to determine the immunophenotypic features of these cases. The identification of abnormal immunophenotypes could be used for the detection of minimal residual disease (MRD). Ninety-three adult patients with de novo acute myeloid leukemia (AML) were analyzed by Southern blot in order to detect MLL rearrangements (MLL+). RT-PCR and genomic long-range PCR were performed to further characterize MLL partial tandem duplication (PTD) in those patients in whom conventional karyotype did not show 11q23 chromosomal translocations. All the patients were homogeneously immunophenotyped at diagnosis. MLL rearrangements were detected in 13 (14%) patients. Four patients (5%) showed 11q23 translocations by karyotypic conventional analysis. Nine patients (10%) revealed PTD of MLL and one patient showed a MLL cleavage pattern. The MLL+ patients usually expressed myeloid and monocytic antigens CD33 (12/13 cases), CD13 (9/13), CD117 (9/13), CD64 (11/13) and in some cases CD14 (4/11). HLA-DR was also positive in (12/13). Eight out of 13 cases expressed the stem cell marker CD34. Only one patient revealed lymphoid marker reactivity (CD7) and CD56 was expressed in 5/13 cases. All the MLL+ patients showed at least one aberrant phenotype at diagnosis, which allowed us to set out a simple panel for the MRD studies. Twenty-seven samples from eight patients in morphologic complete remission (CR) were analyzed using the aberrant immunologic combinations detected at diagnosis. Phenotypically abnormal cells were detected in all the patients who subsequently relapsed, whereas only one patient with MRD+ remained in CR. Owing to the high level of residual leukemic cells, the MLL+ patients showed a short CR duration and a poor survival. In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.

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Characterization of acute myeloid leukemia with MLL rearrangements – no increase in the incidence of coexpression of lymphoid-associated antigens on leukemic blasts

Cited by 13 publications

References 27 publications

Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23

Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23

Antigen expression patterns reflecting genotype of acute leukemias

Acute myeloid leukemia with MLL rearrangements: clinicobiological features, prognostic impact and value of flow cytometry in the detection of residual leukemic cells

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