CD22 Exon 12 deletion is a characteristic genetic defect of therapy-refractory clones in paediatric acute lymphoblastic leukaemia.
Gene expression profiling (GEP) of primary leukaemic cells (PLC) from 157 paediatric B-lineage acute lymphoblastic leukaemia (ALL) patients, including a direct comparison of matched pair initial diagnosis versus first relapse leukaemic specimens, provided previously unknown evidence that relapse clones are characterized by significantly higher expression levels of a CD22 exon 12 deletion (CD22ΔE12)-associated signature transcriptome than the PLC from newly diagnosed patients. In agreement with and validating these GEP results, reverse transcription polymerase chain reaction and Western blot analysis of PLC from 19 of 19 paediatric ALL patients in first bone marrow relapse occurring within 12 months of the completion of primary therapy confirmed them to be CD22ΔE12(+). Likewise, PLC in diagnostic initial bone marrow specimens from seven of seven therapy-refractory newly diagnosed paediatric B-lineage ALL patients with <7 months event-free survival (EFS), including four patients with induction failures and three patients with early relapses, were CD22ΔE12(+), whereas PLC from only one of five newly diagnosed paediatric B-lineage ALL patients with >18 months EFS was CD22ΔE12(+). CD22ΔE12(+) could be detected in PLC of therapy-refractory patients both at the time of initial diagnosis as well as at the time of documented treatment failure. Our study implicates the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy-refractory paediatric B-lineage ALL.
Division of Hematology-Oncology, Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Hong
H
Ma
Sanjive
S
Qazi
Zahide
Z
Ozer
Paul
P
Gaynon
Gregory H
GH
Reaman
Fatih M
FM
Uckun
D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005091:Exons; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D007438:Introns; D009690:Nucleic Acid Conformation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D012322:RNA Precursors; D012333:RNA, Messenger; D012008:Recurrence; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics*; D059467:Transcriptome
D012322:RNA Precursors; D012333:RNA, Messenger; D051918:Sialic Acid Binding Ig-like Lectin 2