Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia.
Acute lymphoblastic leukemia (ALL) cells at relapse are frequently more resistant to treatment than primary clones and this may be caused by further genetic changes in the ALL cells at relapse. These acquired genomic abnormalities have not been fully characterized. To examine the additional genomic alterations of ALL at relapse, we performed single nucleotide polymorphism genomic microarry (SNP-chip) analysis on 14 ALL bone marrow samples at initial diagnosis, remission and relapse. Only two cases at initial diagnosis had a normal appearing genome by SNP-chip. All 14 cases had genomic alterations at relapse; and 10 of these had additional genomic abnormalities not present at diagnosis. Deletion of either the INK4A/ARF gene (2 cases) or the NF2 gene (2 cases) at 22q12.2 was an acquired genomic change at relapse. Loss of heterozygosity with normal copy number [uniparental disomy (UPD)] was detected in 3 cases as an additional genomic change at relapse. Interestingly, several genomic alterations, especially deletions, detected at initial diagnosis, disappeared at relapse, suggesting the ALL cells at relapse were minor clones at initial diagnosis and emerged at relapse. For several cases, trisomy at initial diagnosis changed to either UPD (2 cases) or normal appearing genome (2 cases). Further, we found disruption of PTPRD gene occurring at intron 23 as an additional genomic abnormality in one case. In summary, additional genomic changes are very common events in ALL at relapse; whether these abnormalities are associated with resistance to treatment remains to clarified in further studies.
Kawamata
Norihiko
N
Hematology/Oncology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA 90048, USA. nkawamata@gmail.com
Ogawa
Seishi
S
Seeger
Karl
K
Kirschner-Schwabe
Renate
R
Huynh
Thien
T
Chen
John
J
Megrabian
Nairi
N
Harbott
Jochen
J
Zimmermann
Martin
M
Henze
Günter
G
Schrappe
Martin
M
Bartram
Claus R
CR
Koeffler
H Phillip
HP
D020823:ADP-Ribosylation Factor 1; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015973:Gene Expression Regulation, Leukemic; D016515:Genes, Neurofibromatosis 2; D015894:Genome, Human; D006801:Humans; D007223:Infant; D007621:Karyotyping; D019656:Loss of Heterozygosity; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D024182:Uniparental Disomy
D019941:Cyclin-Dependent Kinase Inhibitor p16; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D020823:ADP-Ribosylation Factor 1