Acute myeloid leukemia with MLL rearrangements: clinicobiological features, prognostic impact and value of flow cytometry in the detection of residual leukemic cells.
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.
Muñoz
L
L
Department of Hematology, Hospital de la Santa Creu, Sant Pau, Barcelona, Spain.
Nomdedéu
J F
JF
Villamor
N
N
Guardia
R
R
Colomer
D
D
Ribera
J M
JM
Torres
J P
JP
Berlanga
J J
JJ
Fernández
C
C
Llorente
A
A
Queipo de Llano
M P
MP
Sánchez
J M
JM
Brunet
S
S
Sierra
J
J
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015139:Blotting, Southern; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005434:Flow Cytometry; D020440:Gene Duplication; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011519:Proto-Oncogenes; D012074:Remission Induction; D014157:Transcription Factors; D014178:Translocation, Genetic
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase