CASE REPORTS in
HAEMATOLOGY (Paper co-edited with the European LeukemiaNet) |
Amplification of MLL gene in a new case of acute myeloid leukemia |
Written | 2010-05 | Sayf Alkatib, Deborah Schloff, Anwar N Mohamed |
Cytogenetics Laboratory, Pathology Department, Wayne State University School of Medicine, Detroit Medical Center, Detroit MI, USA |
Clinics |
Age and sex : | 75 year(s) old female patient. |
Previous History : | no preleukemia |
no previous malignant disease | |
no inborn condition of note |
Organomegaly : no hepatomegaly ; no splenomegaly ; no enlarged lymph nodes ; no central nervous system involvement |
Blood |
WBC : 3.00 x 109/L ; Hb : 9.0 g/dL ; platelets : 37.000 x 109/L; blasts : 18% % . |
Bone marrow : 90 Hypercellular (90%) bone marrow with at least 30% blasts. There was dysplasia in all three cell lines. |
Cyto pathology classification |
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 |
Date of diagnosis: 09-2009 |
Treatment : Gemtuzumab Ozogamicin, and 5-Azacitidine. |
Complete remission : None |
Status : Dead 11-2009 |
Survival : 2 month(s) |
Karyotype |
Sample : Bone marrow aspirate ; culture time : 24 h, 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 molecular 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. |
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G-banded karyotype showing 45,X,add(X)(q22),-3,del(5)(q13q33), hsr(11)(q23),add(12)(p11.2),-17,+r[cp20]. |
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FISH with LSI MLL/11q23 probe showing amplification of MLL gene (arrow) along with one normal copy. |
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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 |
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. |
Internal links |
Atlas Card | MLL amplification in leukemia |
Bibliography |
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Citation |
This paper should be referenced as such : |
Free journal version : [ pdf ] [ DOI ] |
On line version : http://AtlasGeneticsOncology.org/Reports/MLLMohamedID100045.html |
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