Amplification of MLL gene in a new case of acute myeloid leukemia

Sayf Alkatib, Deborah Schloff, Anwar N Mohamed Affiliation

Cytogenetics Laboratory, Pathology Department, Wayne State University School of Medicine, Detroit Medical Center, Detroit MI, USA

Previous history

Preleukaemia

Malignant disease

Inborn condition

Clinics case report

Age

75 yrs

Sex

Liver

Spleen

Lymph nodes

Cns involv

Blood data

Wbc

3.00

9.0

Platelets

37.000

Blasts

18%

Bone marrow

90 Hypercellular (90%) bone marrow with at least 30% blasts. There was dysplasia in all three cell lines.

Cyto path

Cytology

MDS/AML

Immunophenotype

Flow cytometry identified a population of blasts of myeloid origin encompassing 31% of cells. The blasts were expressing CD13, CD33, CD34, CD117, HLA-DR, and CD56.

Rearranged ig tcr

Not performed.

Pathology

Increased and poorly maturing myeloid leukogenesis. Increased erythrocytogenesis with dysplastic forms (nuclear budding and megaloblastoid changes). Megakaryocytogenesis was markedly increased with dysplastic forms (hypolobulated and multiple widely separated nuclei).

Electron microscopy

Not performed.

Precise diagnosis

Acute myeloid leukemia with multilineage dysplasia.

Survival data

Date diagnosis

09-2009

Treatment

Gemtuzumab Ozogamicin, and 5-Azacitidine.

Complete remission

None

Status

Date last follow

11-2009

Survival

Karyotype

Sample

Bone marrow aspirate

Culture time

24h without stimulating agents and 48hr with 10% conditioned medium

Banding

GTG.

Results

Analysis of 20 metaphase cells revealed an abnormal female karyotype in all metaphases. Very complex chromosomal abnormalities were identified. karyotype was designated; 45,X,add(X)(q22),-3,del(5)(q13q33),hsr(11)(q23),add(12)(p11.2),-17,+r[cp20].

Other molec studies

Technics

Fluorescence in situ hybridization (FISH) using the LSI EGR1/(5q31)/ D5S23:D5S721 dual color, LSI MLL/11q23 dual color breakapart DNA probes, and whole chromosome paint (WCP) 11 was performed (Vysis Inc. Downers Grove, IL).

Results

Deletion of EGR1/5q31 was seen in 25% of cells and amplification of MLL/11q23 gene was found in 60% of cells. MLL signals appeared fused indicating lack of MLL rearrangement.

Images

G-banded karyotype showing 45,X,add(X)(q22),-3,del(5)(q13q33), hsr(11)(q23),add(12)(p11.2),-17,+r[cp20].

FISH with LSI MLL/11q23 probe showing amplification of MLL gene (arrow) along with one normal copy.

WCP 11 spectrum green on the same metaphase in figure 2 showing two painting signals indicating that the amplified MLL located on chromosome 11 (arrow).

Comments section

Comments

The case described here is of a 75-year-old female who was diagnosed with AML with multilineage dysplasia. Cytogenetics revealed a complex aberrant karyotype (CAK) including deletion of 5q and loss of chromosome 17. In addition, FISH confirmed deletion of EGR1/5q31 and showed amplification of MLL/11q23 gene in the form of hsr at 11q. Literature suggests an association of amplification of MLL with CAK. Moreover, deletions of 5/5q and 17/17p, such as in our case, are frequently found along with MLL amplification. Previously reported AML cases with MLL amplifications tend to occur in elderly patients, and are characterized by rapid progression, poor response to treatment, and poor clinical outcome. The present case supports the notion that MLL amplification is commonly found in the setting of CAK with deletion of chromosome 5 and 17. Thus, the presence of MLL amplification along with deletion 5q in AML cases appears to be a genomic pattern which signifies a poor prognosis in elderly patients.

Bibliography

Pubmed ID	Last Year	Title	Authors
10918392	2000	MLL amplification in myeloid leukemias: A study of 14 cases with multiple copies of 11q23.	Michaux L et al
12034519	2002	MLL amplification in myeloid malignancies: clinical, molecular, and cytogenetic findings.	Dolan M et al
12946992	2004	Expression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies.	Poppe B et al
14978788	2004	Distinct sequences on 11q13.5 and 11q23-24 are frequently coamplified with MLL in complexly organized 11q amplicons in AML/MDS patients.	Zatkova A et al
16026782	2005	Oncogene amplification in transforming myelodysplasia.	Papenhausen PR et al
16425025	2006	Del(5q) and MLL amplification in homogeneously staining region in acute myeloblastic leukemia: a recurrent cytogenetic association.	Herry A et al
17452254	2007	MLL amplification in acute myeloid leukemia.	Pajuelo-Gámez JC et al
19480936	2009	Association of MLL amplification with poor outcome in acute myeloid leukemia.	Maitta RW et al
19306356	2009	AML/MDS with 11q/MLL amplification show characteristic gene expression signature and interplay of DNA copy number changes.	Zatkova A et al

Citation

Sayf Alkatib, Deborah Schloff, Anwar N Mohamed

Amplification of MLL gene in a new case of acute myeloid leukemia

Atlas Genet Cytogenet Oncol Haematol. 2010-05-01

Online version: http://atlasgeneticsoncology.org/case-report/208843/amplification-of-mll-gene-in-a-new-case-of-acute-myeloid-leukemia