The Bcr-Abl tyrosine kinase regulates several Bcl-2 family proteins that confer resistance to apoptosis in chronic myeloid leukemia (CML) cells. Given p53's ability to modulate the expression and activity of Bcl-2 family members, we hypothesized that targeting Bcr-Abl, Bcl-2, and p53 concomitantly could have therapeutic benefits in blast crisis (BC) CML and in quiescent CML CD34+ cells that are...

Chronic myeloid leukemia (CML), a hematopoietic stem cell disorder, cannot be eradicated by conventional chemotherapy or the tyrosine kinase inhibitor (TKI) imatinib mesylate (IM). To target CML stem/progenitor cells we investigated BMS-214662, a cytotoxic farnesyltransferase inhibitor, previously reported to kill non-proliferating tumor cells. IM or dasatinib alone reversibly arrested prolifer...

Our study is designed to assess if exosomes released from chronic myelogenous leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM-1 and VCAM-1 cell adhesion molecules and interleukin-8 expression. The ...

Primitive quiescent CD34(+) chronic myeloid leukemia (CML) cells are more biologically resistant to tyrosine kinase inhibitors than their cycling counterparts; however, graft-versus-leukemia (GVL) effects after allogeneic stem cell transplantation (SCT) probably eliminate even these quiescent cells in long-term surviving CML transplant recipients. We studied the progeny of CD34(+) cells from CM...

Chronic myelogenous leukemia (CML) requires the BCR/ABL tyrosine kinase for disease onset and maintenance. As a result, CML can be successfully treated with tyrosine kinase inhibitors (TKIs) such as imatinib. Most patients are maintained in a disease-suppressed state on daily TKI therapy for several years and in many cases this treatment prevents progression to the blast phase. If the TKI is di...

Chronic myeloid leukemia (CML) is a clonal hematological disease that represents 15-20% of all adult leukemia cases. The study and treatment of CML has contributed pivotal advances to translational medicine and cancer therapy. The discovery that a single chromosomal abnormality, the Philadelphia (Ph) chromosome, is responsible for the etiology of this disease was a milestone for treating and un...

Chronic myelogenous leukemia (CML) results from malignant transformation of a primitive hematopoietic cell by the BCR/ABL oncogene. The breakpoint cluster region/ABL (BCR/ABL) tyrosine kinase inhibitor imatinib mesylate (imatinib) is highly effective in inducing remissions in CML. However, the effects of imatinib on intracellular signaling in primary progenitor cells are not well described. We ...

We generated a homogeneous population of cells with cytotoxic activity termed "adherent lymphokine-activated killer" (ALAK) cells from the peripheral blood of nine patients in the chronic phase of Ph1 positive chronic myelogenous leukemia (CML). The selective enrichment of CML ALAK cells depended on their propensity to adhere to plastic and proliferate when cultured in the presence of recombina...

Age-related macular degeneration (AMD) causes severe vision loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein N -carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation end products that are abundant in Bruch mem...

...........................................................................................................................7 Introduction .....................................................................................................................9 Review of the literature ..................................................................................................10 1. History of ...