Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

Abstract

Leukemia associated antigens (LAAs) are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL) cloning, serological analysis of recombinant cDNA expression libraries (SEREX) and mass spectrometry (MS). In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs), serial analysis of gene expression (SAGE) and 2-dimensional gel electrophoresis (2-DE) have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML). It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel) and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.

Overexpression of Bcl2 protein predicts chemoresistance in acute myeloid leukemia: Its correlation with FLT3

“…This has lead to lack of efficient biomarkers in clinical diagnosis in AML. Biomarkers are required to enable identification of patients who are most likely to benefit from specific treatments and to help improve clinical outcome and treatment design [3]. Potential therapeutic targets and prognostic biomarkers of AML patients can be identified by understanding the cellular pathways and molecular changes involved in malignant transformation.…”

Leukocytosis in an Infant With Down Syndrome

“…12 It has been identified as a marker specifically in AMKL-M7 in patients with DS. 3,13 At the present time, PRAME is not routinely used as part of the diagnostic workup. GATA-1 and PRAME genetic markers have the potential to serve as parameters for disease course prediction, diagnostic purpose, and response to therapy for TL.…”

“…GATA-1 and PRAME genetic markers have the potential to serve as parameters for disease course prediction, diagnostic purpose, and response to therapy for TL. 3,13…”

Costimulation Immunotherapy in Infectious Diseases

“…92a,92b,92c Latest reports suggest that 4-1BBL can provide a costimulatory signal to the human CD28-T cells, leading to cytokine production, cell survival and the upregulation of molecules associated with cellular cytotoxicity. 98 These findings suggest that 4-1BBL, rather than B7, may be the better choice of immune stimulatory agents to use in an immunotherapeutic regimen for antiviral immunity. 94,95 The proportion of T cells lacking CD28 is increased in people with chronic viral infections or other persistent conditions such as multiple myeloma.…”