Abstract：
:Relapse following remission induction chemotherapy remains a barrier to survival in approximately 20% of children suffering from acute lymphoblastic leukemia (ALL). To investigate the mechanism of relapse, 27 matched diagnosis and relapse ALL samples were analyzed for clonal populations using polymerase chain reaction (PCR)-based detection of multiple antigen receptor gene rearrangements. These clonal markers revealed the emergence of apparently new populations at relapse in 13 patients. More sensitive clone-specific PCR revealed that, in 8 cases, these "relapse clones" were present at diagnosis and a significant relationship existed between presence of the relapse clone at diagnosis and time to first relapse (P < .007). Furthermore, in cases where the relapse clone could be quantified, time to first relapse was dependent on the amount of the relapse clone at diagnosis (r = -0.84; P = .018). This observation, together with demonstrated differential chemosensitivity between subclones at diagnosis, argues against therapy-induced acquired resistance as the mechanism of relapse in the informative patients. Instead these data indicate that relapse in ALL patients may commonly involve selection of a minor intrinsically resistant subclone that is undetectable by routine PCR-based methods. Relapse prediction may be improved with strategies to detect minor potentially resistant subclones early during treatment, hence allowing intensification of therapy.
journal_name
Bloodjournal_title
Bloodauthors
Choi S,Henderson MJ,Kwan E,Beesley AH,Sutton R,Bahar AY,Giles J,Venn NC,Pozza LD,Baker DL,Marshall GM,Kees UR,Haber M,Norris MDdoi
10.1182/blood-2007-01-067785subject
Has Abstractpub_date
2007-07-15 00:00:00pages
632-9issue
2eissn
0006-4971issn
1528-0020pii
blood-2007-01-067785journal_volume
110pub_type
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