title: Philadelphia-positive acute lymphoblastic leukemia with multiple subclones including duplication of the Philadelphia chromosome and Abelson oncogene.
abstract: A case of Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL) with multiple subclones including duplication of the BCR-ABL1 fusion gene and of the Abelson oncogene (ABL1) is reported. Cytogenetically, two different rearrangements of chromosome 9 not involved in the t(9;22) were found in two subclones. In one subclone the normal 9 was lost and replaced by an acrocentric marker, which contained an additional copy of the BCR-ABL1 fusion gene. Reverse transcriptase polymerase chain reaction detected the fusion transcripts p210 (e13a2 junction) and p190 (e1a2 junction), whereas fluorescence in situ hybridization showed the major BCR-ABL1 junction in both Ph chromosomes, strongly suggesting that the presence of the p210 and p190 proteins in this case was due to mechanisms of alternative or mis-splicing at the transcriptional level. The second subclone showed the classic t(9;22) plus an add(9)(p24) containing two copies of the ABL1 gene. Other molecular events involving chromosome 9 were a monoallelic loss of JAK2 in both subclones and an additional loss of P15/P16 in the subclone with the acrocentric marker bearing the extra Ph chromosome.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, University of Perugia, Policlinico Monteluce, 06100, Perugia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: La Starza
authors.forename: Antonella
authors.initials: A
authors.lastname: Vitale
authors.forename: Anna
authors.initials: A
authors.lastname: Serra
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fioritoni
authors.forename: Daniela
authors.initials: D
authors.lastname: Falzetti
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D015139:Blotting, Southern; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D002999:Clone Cells / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D020440:Gene Duplication; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics; D010677:Philadelphia Chromosome; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D015513:Oncogene Proteins; D016044:Fusion Proteins, bcr-abl