Therapy-related adult acute lymphoblastic leukemia with t(4;11)(q21; q23): MLL rearrangement, p53 mutation and multilineage involvement.
A diagnosis of pro-B acute lymphoblastic leukemia (ALL) with CD15+ was made in a 42-year-old woman, 12 months after the treatment of uterine adenocarcinoma by carboplatinum, anthracyclines, etoposide and radiotherapy. Molecular cytogenetic studies revealed a karyotype with multiple chromosome changes, including the t(4;11)(q21;q23) and a 17p-chromosome, with MLL disruption and 17p13/p53 gene deletion in 86% of the cells. A p53 exon 6 mutation was documented, resulting in p53 protein stabilization, with 20% of the cells reacting with the 1801 anti-p53 monoclonal antibody. Dual-color FISH using MLL and p53 probes was performed on peripheral blood smears, providing direct evidence of the involvement of the blast cells and of the granulocytic lineage. Only a partial, shortlasting response was obtained by induction treatment, confirming that a poor prognosis is associated with therapy-related ALL with the 4;11 translocation.
Bigoni
R
R
Dipartimento di Scienze Biomediche e Terapie Avanzate, Università di Ferrara, Italy.
Cuneo
A
A
Roberti
M G
MG
Moretti
S
S
De Angeli
C
C
Dabusti
M
M
Campioni
D
D
del Senno
L
L
Biondi
A
A
Chaplin
T
T
Young
B D
BD
Castoldi
G
G
D000328:Adult; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D016158:Genes, p53; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein; D016609:Neoplasms, Second Primary / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase