Mapping of chromosome 17 breakpoints in acute myeloid leukemias.
The 17q11-21 chromosomal region is frequently involved in non-random structural rearrangements associated with the M1 and M2 subtypes of acute myeloid leukemias (AML), as well as with the 15;17 translocation typical of the promyelocytic subtype. A number of genes have been localized in this region including the c-erbA-1 and c-erbB-2 proto-oncogenes, the genes coding for the granulocyte-colony stimulating factor (G-CSF), the retinoic acid receptor alpha (RAR alpha) and the myeloperoxidase enzyme (MPO). However, the precise location of these genes in relationship to the 17q11-21 breakpoint(s) has not been determined. Using in situ hybridization on metaphase chromosomes, we established the position of the breakpoints in relationship to the c-erbA-1, c-erbB-2, G-CSF, RAR alpha and MPO loci in a series of AML cases bearing 17q11-21 rearrangements. We report: (i) that the respective position of the five genes is centromere - c-erbA-1 - G-CSF - c-erbB-2 - RAR alpha - MPO - telomere; (ii) that the breakpoints of the various AML subtypes are variably located between the centromere and c-erbB-2 in M1 and M2; (iii) that the breakpoints are consistently located between c-erbB-2 and RAR alpha/MPO in M3; and (iv) that the breakpoint on chromosome 17 in the 15;17 translocation is located on 17q21 and not on 17q11-12 as previously reported.
Istituto di Clinica Medica I, University of Perugia, Policlinico Monteluce, Italy.
L
L
Longo
E
E
Donti
A
A
Mencarelli
G
G
Avanzi
L
L
Pegoraro
G
G
Alimena
A
A
Tabilio
G
G
Venti
F
F
Grignani
P G
PG
Pelicci
D000208:Acute Disease; D001853:Bone Marrow / Q000473:pathology; D002460:Cell Line; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D005260:Female; D015321:Gene Rearrangement; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D008297:Male; D009693:Nucleic Acid Hybridization; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D011988:Receptors, Thyroid Hormone
D016179:Granulocyte Colony-Stimulating Factor; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011988:Receptors, Thyroid Hormone