Acute myeloid leukemia with trisomy 11: A molecular cytogenetic study

doi:10.1016/S0165-4608(96)00437-2

Cancer Genetics and Cytogenetics

Volume 99, Issue 1, November 1997, Pages 19-23

https://doi.org/10.1016/S0165-4608(96)00437-2 Get rights and content

Abstract

Trisomy 11 is uncommon in acute myeloid leukemia (AML) and molecular studies have shown partial tandem duplication of the MLL gene in some cases. In a case of AML with trisomy 11, the MLL gene was found to be tandemly duplicated, leading to the formation of a fusion transcript involving splicing of exon 8 to exon 2. Fluorescence in situ hybridization revealed two populations of blasts, with about two-thirds of them showing trisomy 11. These findings suggested that the trisomic and non-trisomic clones had evolved from a clone with a common submicroscopic mutation. As recent studies showed that MLL gene duplication in fact occurs more often as a primary mutation in the absence of trisomy 11, it is possible that in our case the MLL gene duplication might be the common underlying mutation. The clinical course of this case was similar to the poor prognosis reported for trisomy 11.

References (14)

Y. Gu et al.
The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene
Cell
(1992)
D.C. Tkachuk et al.
Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias
Cell
(1992)
Primary, single autosomal trisomies associated with hematological disorders
Leukemia Res
(1992)
M.L. Slovak et al.
Trisomy 11: an association with stem/progenitor cell immunophenotype
Br J Haematol
(1995)
M. Djabali et al.
A trithorax-like gene is interrupted by chromosome 11q234 translocations in acute leukemias
Nature Genet
(1992)
M.A. Caligiuri et al.
Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocation
Cancer Res
(1994)
S.A. Schichman et al.
ALL-1 partial duplication in acute leukemia

There are more references available in the full text version of this article.

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Hematological, immunophenotypic, and cytogenetic characteristics of acute myeloblastic leukemia with trisomy 11
2005, Cancer Genetics and Cytogenetics
Citation Excerpt :
The clinical and hematological profile of patients with clonal trisomies in acute myeloblastic leukemia (AML) have not been well characterized, even though patients with isolated trisomies account for approximately 11% of all karyotypically aberrant AML cases published [2]. Trisomy 11 has been reported in both de novo and secondary acute myeloid leukemias and myelodysplastic syndromes (MDS) and it is the third most common sole trisomy in de novo AML [2,3]; however, AML cases with trisomy 11 have been usually reported as a part of large series of AML patients, and the information on the specific disease characteristics of this AML variant is limited [2–7]. In the present study, we analyzed the clinical, biological, immunophenotypic, and cytogenetic characteristics, as well as the outcome, of 15 AML patients with trisomy 11 at diagnosis.
We evaluated the incidence of trisomy 11 in acute myeloblastic leukemia (AML) and its correlation with the most relevant clinical, biological, and immunophenotypic disease characteristics in a total of 399 consecutive AML patients. Trisomy 11 was found in 15 patients (3.8%), in 3 of them as the sole abnormality. Median age was 68 years (range 48–87); 87% of patients were older than 60 years. Seven patients displayed multilineage dysplasia. Cytogenetics showed an association with trisomy 8 in six patients, and in five cases with a del(5q); nine patients had complex karyotypes. In all cases, in situ hybridization studies revealed three copies of the MLL gene, but no rearrangements or tandem duplications of MLL. Immunophenotypic analysis of blast cells showed a constant immature immunophenotypic profile with CD34 or CD117 expression (or both) in all cases analyzed. The complete remission rate was 43%; median survival time was only 2 months.
A rapidly progressive chronic myeloproliferative disease with isolated trisomy 6 [2]
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The occurrence of trisomy 4 or trisomy 10 as the sole chromosomal abnormality in acute myeloid leukemia (AML) is very rare, the reported frequency being less than 1%. We describe two cases of AML-M2 with concomitant trisomy 4 and trisomy 10, a hitherto undescribed phenomenon. They showed two unusual features, including immunoreactivity for CD56 and a short-lived but rapidly progressive myelodysplastic phase preceding the appearance of frank leukemia. These findings raise the possibility that AML with concommitant trisomy 4 and trisomy 10 may constitute a distinctive subtype of AML.
Routine fluorescence in situ hybridization with the MLL probe does not reliably detect two separate signals on one chromosome 11 in patients with trisomy 11
2001, Cancer Genetics and Cytogenetics
Trisomy 11 is considered to be a rare cytogenetic abnormality in myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). Duplication of the MLL gene (localized to 11q23) has been found on one chromosome 11 in patients with trisomy 11, detected by DNA techniques. We investigated copy number of MLL in seven patients with trisomy 11 to see if duplication could be assessed by the detection of two separate signals on fluorescence in situ hybridization (FISH). If so, FISH could provide a quick easy screen of MLL status in routine referrals. The diagnostic bone marrow aspirate showed trisomy 11 in five adult patients with MDS/AML as part of a complex karyotype and in two children with acute lymphoblastic leukemia (ALL) as part of a hyperdiploid karyotype. Fluorescence in situ hybridization utilized the suspensions remaining after the cytogenetic harvest. Two FISH probes were used on the adult patients (MLL - Oncor and Vysis), and one (Vysis) for the two children with ALL. Analysis showed that the proximity of the two putative hybridization signals made it very difficult to unambiguously see two separate signals. The hybridisations (Oncor probe) were convincing of MLL duplication (namely two distinct signals) in only one patient, but this was not borne out with the other MLL probe (Vysis). We conclude that conventional FISH with MLL probe is not suited to act as a screen for MLL duplication in patients with trisomy 11.
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2001, Best Practice and Research: Clinical Haematology
The standard Philadelphia (Ph) translocation t(9;22), its variants and a proportion of Ph-negative cases are positive for the BCR-ABL fusion gene, as determined by molecular analysis. Extensive deletions of chromosome 9 and 22 derived sequences around the translocation breakpoints on the derivative 9 are seen in 10–30% of patients at diagnosis and may confer a worse prognosis. Additional cytogenetic changes can occur in the few months before or during disease progression and are often specific for blast morphology; however, the molecular basis of the most common additional cytogenetic abnormalities is largely unknown. Cytogenetics is important for monitoring patient response to treatment but is increasingly being replaced by the more sensitive and less invasive techniques of RT-PCR and FISH.

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Cancer Genetics and Cytogenetics

Abstract

References (14)

The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene

Cell

Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias

Cell

Primary, single autosomal trisomies associated with hematological disorders

Leukemia Res

Trisomy 11: an association with stem/progenitor cell immunophenotype

Br J Haematol

A trithorax-like gene is interrupted by chromosome 11q234 translocations in acute leukemias

Nature Genet

Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocation

Cancer Res

ALL-1 partial duplication in acute leukemia

Cited by (18)

Chromatin modifier enzymes, the histone code and cancer

Hematological, immunophenotypic, and cytogenetic characteristics of acute myeloblastic leukemia with trisomy 11

A rapidly progressive chronic myeloproliferative disease with isolated trisomy 6 [2]

Acute myeloid leukemia with concomitant trisomies 4 and 10: A distinctive form of myeloid leukemia?

Routine fluorescence in situ hybridization with the MLL probe does not reliably detect two separate signals on one chromosome 11 in patients with trisomy 11

Cytogenetics of chronic myeloid leukaemia

Original articleAcute myeloid leukemia with trisomy 11: A molecular cytogenetic study

Abstract

Cell

Cell

Primary, single autosomal trisomies associated with hematological disorders

Leukemia Res

Trisomy 11: an association with stem/progenitor cell immunophenotype

Br J Haematol

A trithorax-like gene is interrupted by chromosome 11q234 translocations in acute leukemias

Nature Genet

Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocation

Cancer Res

ALL-1 partial duplication in acute leukemia

Original article
Acute myeloid leukemia with trisomy 11: A molecular cytogenetic study