Farahnaz Haftlang

CML has become the paradigm for targeted cancer treatment. The introduction of imatinib has led to a dramatic improvement of prognosis in chronic phase patients when compared to conventional chemotherapy. The use of small molecule kinase inhibitors has been extended to other entities, and thereby redefined the management of cancer, in general. By virtue of their specific mode of action and the addiction of CML to BCR-ABL, resistance to therapeutic kinase inhibitors is based on a limited number...

Shared Tumor Antigen Peptide Vaccines

Another active-specific immunotherapy with potential antitumor effect in CML relies on the use of intracellular proteins other than p210. In fact a number of self proteins are aberrantly overexpressed in CML and other tumor cells while being expressed at low levels in normal lineages and thus may function as targets for directed immunotherapy of residual disease. As in the case of p210, despite the intracellular location of these proteins, short peptides produced by their cellular processing...

Clinical Development Of Dasatinib In Chronic Myeloid Leukemia

Dasatinib was first investigated in a phase I dose-escalating study involving patients with CML in all phases who had failed or developed intolerance to imati-nib therapy (Table 1). Initially, dasatinib was administered only to patients with CP on a once-daily schedule for five consecutive days, followed by two days without treatment every week, and later a twice-daily administration was also investigated as well as a continuous daily administration. After clinical activity was observed in CP,...

References

Cortes J, Talpaz M, O'Brien S, et al. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res 2005 11(9) 3425-3432. 2. Cortes J, O'Brien S, Kantarjian H. Discontinuation of imatinib therapy after achieving a molecular response. Blood 2004 104(7) 2204-2205. 3. Graham SM, Jorgensen HG, Allan E, et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to...

Adaphostin Tyrosine Kinase Inhibitor Or Nontyrosine Kinase Inhibitor

Adaphostin NSC 680410, National Cancer Institute, Bethesda, Maryland, U.S.A. is the adamanyl ester of the tyrphostin, AG957 10 . Tyrphostins are a group of structurally diverse compounds that were synthesized and evaluated as potential inhibitors of tyrosine kinases. AG957 was identified as a non-ATP inhibitor of p210Bcr-Abl 11 , which interfered with the binding of protein substrates to this tyrosine kinase. Several lines of evidence suggest that, currently, adaphostin should be considered as...

Jorge Cortes Cml University Hospital Of Texas

Chronic myeloid leukemia CML is a rare disease and yet it has had a profound impact on the development of modern, evidence-based medicine. Some 160 years ago the term leukemia was coined when Bennet, and almost simultaneously Virchov, described the striking white appearance of the blood of two patients with, presumably, CML. The discovery of the Philadelphia chromosome Ph , first described as a minute chromosome 22 by Nowel and Hungerford in 1960, marks the first consistent association between...

True Chronic Myeloid Leukemia Specific Antigen Vaccines

Tumor Associated Antigen Definition

The BCR-ABL-derived p210 protein and particularly the alternative b3a2 or b2a2 peptide epitope at its fusion point is the most obvious CML-specific target, and thus was first explored for a vaccine strategy. p210 is exclusive to the CML clone, and the sequences of amino acids contained in the b3a2 and b2a2 junctional regions represent unique tumor-specific determinants, which can be exploited for an immunological attack against the tumor cell 11 . Recent data support the hypothesis that...