Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene status.
In this study we investigated the presence of structural lesions in the ALL-1, p53 and p16 (cyclin-dependent kinase 4 inhibitor) genes in leukaemic cells obtained from 22 patients with infant acute leukaemia (aged < 18 months). Of these, 18 cases were classified as acute lymphoblastic leukaemia (ALL) and four as acute myeloid leukaemia (AML). Tumour DNAs were analysed by a combination of Southern blot. polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequence analyses. The results showed ALL-1 gene rearrangements in 15/22 (68%) cases, p53 gene mutations in 5/22 (26%), and a homozygous deletion of p16 in a single T-ALL case. p53 and p16 alterations were all found in the group of patients with ALL-1 gene rearrangements. p53 mutations were more often associated with a myeloid phenotype (3/5). In summary, multiple molecular alterations were found in 6/15 (40%) infant acute leukaemias with ALL-1 rearrangements. As to the clinical course, patients with additional lesions had similar clinical outcome with respect to patients with ALL-1 gene rearrangement as the sole genetic aberration. This may support the hypothesis that ALL-1 alterations are genetic events per se sufficient to confer a fully malignant phenotype to the leukaemic clone.
Cimino
G
G
Ematologia, Dipartimento di Biopatologia Umana, Universtità degli Studi La Sapienza di Roma, Rome, Italy.
Lanza
C
C
Elia
L
L
Lo Coco
F
F
Gaidano
G
G
Biondi
A
A
Pastore
C
C
Serra
A
A
Canaani
E
E
Croce
C M
CM
Mandelli
F
F
Saglio
G
G
D000208:Acute Disease; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005091:Exons; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D007621:Karyotyping; D007945:Leukemia, Lymphoid / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16