Complex Chromosomal Abnormalities in TEL-AML1-Positive Acute Lymphoblastic Leukemia Is Associated with High White Blood Cell Count in Pediatric Patients.
Yao Schmidt, Amy McGranahan, Xiayuan Liang. The Children's Hospital, Aurora, CO; University of Colorado Denver School of Medicine, Aurora
Background: TEL-AML1 (ETV6-RUNX1) is a recurrent genetic abnormality in B-acute lymphoblastic leukemia (ALL) and is usually associated with a favorable outcome in pediatric patients. Most of cases with TEL-AML1 have a simple cryptic translocation and show a normal karyotype by conventional cytogenetic analysis with detection of TEL-AML1 by FISH and/or RT-PCR. A subset of cases has other chromosomal abnormalities in addition to TEL-AML1, and some of these cases have complex karyotypes. Also, some cases with TEL-AML1 are clinically more aggressive than others. To investigate if additional cytogenetic abnormalities play a role in an aggressive disease process, we examined karyotype, S-phase fraction (SPF, a cell proliferation indicator), and white blood cell count (WBC) in a series of B-ALL with TEL-AML1translocation in pediatric patients.
Design: 50 cases of B-ALL with TEL-AML1 at The Children's Hospital, Colorado from 2000 to 2010 which have a complete karyotype available are included in this study. The complex karyotype is defined as ≥ 3 chromosomal structural abnormalities in addition to TEL-AML1 or ≥ 2 abnormal clones with ≥ 3 additional chromosomal structural abnormalities. TEL-AML1 translocation was tested by either FISH and/or RT-PCR study. SPF was analyzed by flow cytometry. SPF >10% was defined as a high SPF.
Results: Cases with complex karyotypes more frequently carry high WBC (> 50,000) than cases with normal karyotypes (P = 0.044). A high cell proliferation rate also is seen more often in cases with complex karyotypes than cases with normal karyotypes.
|TEL-AML1 translocation||# of Cases||S-phase (>10%)||WBC (>50,000/mm3)||P value|
|Normal karyotype(simple cryptic TEL-AML1)||27||2/24 (8%)||3/27 (11%)|
|Non-complex karyotype||14||1/13 (8%)||1/14 (7%)|
|Complex karyotype||9||2/9 (22%)||4/9 (44%)||0.044|