Publication Date:
2019-11-13
Description:
Cell surface antigen expression in AML is becoming focus of investigation as it relates to prognostic impact as well as potential therapeutic implications. The CD117 (c-KIT) receptor tyrosine kinase is expressed on the cell surface of hematopoietic stem cells and its signaling is important in cell survival, proliferation and differentiation. CD117 is expressed in a majority of AML cases. In addition, mutations in c-KIT have been identified in a subset of patients, specifically those with CBF AML (inv(16)/t(16;16) and t(8;21)). As there is increasing interest in using tyrosine kinase inhibitors with anti-KIT activity based on surface CD117 expression as treatment in AML, we sought to evaluate the association of CD117 expression with biologic and clinical features in pediatric and young adult (YA) AML. A total of 1803 pediatric and YA patients (ages 0.01-29.2 years) treated on the Children's Oncology Group (COG) phase III trials AAML0531 (n=762) and AAML1031 (n=1041) with complete cyto/molecular and outcome data available were included in the analysis. The primary aim of AAML0531 evaluated the addition of gemtuzumab ozogamicin to a 5-course MRC-based backbone, while AAML1031 evaluated the addition of bortezomib to a similar 4-course backbone. Outcomes between the 2 primary randomized arms on each trial were similar and thus were included together for each trial. Multidimensional flow cytometry was used to determine the CD117 mean fluorescence intensity (MFI) of myeloid progenitor cells as defined by CD45 low and side scatter using a CD117-PE antibody with stable intensity detection since 2002. Patients were divided into quartiles based on CD117 expression and clinical characteristics and outcome were evaluated across the quartiles. CD117 MFI distribution was similar across both trials (Fig 1A). Analysis of CD117 expression with cytogenetics demonstrated that t(8;21) was significantly associated with higher CD117 (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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