Molecular analysis of six variant Philadelphia chromosome translocations in chronic myeloid leukemia.
In 420 Philadelphia positive (Ph+) chronic myeloid leukemia (CML) patients karyotyped at diagnosis in our laboratory, 26 Ph variants (6.2%) were observed. Twelve of them are reported. Five cases are "simple" variants without detectable involvement of band 9q34, and seven are "complex," since a third chromosomal band is involved in the Ph formation. Two translocations [t(7;22)(q36;q11) and t(9;22;12)(q34;q11;q11)] are reported for the first time. Six cases were characterized molecularly, and bcr-abl rearrangement was demonstrated, confirming involvement of 9q34 band also in the cases in which chromosomes 9 appear cytogenically normal. Chimeric mRNAs in which M-BCR exon 3 is joined to abl exon 2 (type b3-a2) were detected in four of six cases; one case showed a DNA breakpoint in zone III, which may also give rise to the same transcript. In one case, mRNA junction was b2-a2. The frequency of the b3-a2 junction occurs more frequently in CML patients with a Ph variant than in patients with the standard translocation, suggesting a preferential correlation between this type of transcript and the involvement of other chromosomes in Ph formation.
Sessarego
M
M
Dipartimento di Medicina Interna, Università di Genova, Italy.
Martinelli
G
G
Chiamenti
A
A
Defferrari
R
R
Fugazza
G
G
Bruzzone
R
R
Ajmar
F
F
Pignatti
P F
PF
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002872:Chromosome Deletion; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010677:Philadelphia Chromosome; D014178:Translocation, Genetic / Q000235:genetics*