Drug resistance in myeloid leukemias may be mediated by an increased capacity to repair chemotherapy-induced DNA damage. Some tumor cell lines that are resistant to nitrosoureas contain the DNA repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase). This protects cells by removing cytotoxic, nitrosourea-induced O6-alkylguanine adducts. We measured the level of alkyltransferase a...

Recently, low-molecular-weight B-cell growth factor (LMW-BCGF) has been reported to stimulate growth of leukemic cells from B-cell precursor-acute lymphoblastic leukemia (BCP-ALL). We further investigated the effects of LMW-BCGF on proliferation of leukemic clonogenic (progenitor) and nonclonogenic (progeny) cells from children with BCP-ALL (28 patients) and B-cell ALL (two patients). Patients ...

BACKGROUND The assessment of anticancer agents to treat leukemia needs to have animal models closer to the human pathology such as implantation in immunodeficient mice of leukemic cells from patient samples. A sensitive and early detection of tumor cells in these orthotopic models is a prerequisite for monitoring engraftment of leukemic cells and their dissemination in mice. Therefore, we devel...

After achieving remission, approximately one-third of patients with T-cell acute lymphoblastic leukemia (T-ALL) relapse due to the resurgence of residual leukemic cells that cannot be detected in remission by morphologic methods. Thus, the early detection of residual disease is highly desirable to monitor the efficacy of therapy, or to institute an alternative mode of therapy. Toward this aim, ...

BACKGROUND Disease recurrence in patients with acute myeloid leukemia may be partially explained by the escape of leukemic blasts from CD4(+) T-cell recognition. The current study investigates the role of aberrant HLA class II antigen presentation on leukemic blasts by determining both the clinical and functional impact of the class II-associated invariant chain peptide (CLIP). DESIGN AND MET...

The concept of tumor immunosurveillance has raised prospects for natural killer cell-based immunotherapy of human cancer. The cure of acute myeloid leukemia may depend on eradication of leukemic stem cells, the self-renewing component of leukemia. Whether natural killer cells can recognize and lyse leukemic stem cells is not known. To develop strategies that effectively target acute myeloid leu...

We compared the pharmacokinetics of daunomycin (7.5 mg/kg i.v. bolus injection) in normal and leukemic rats using a leukemia model which resembles acute myeloid leukemia in humans. Due to a more rapid decrease in plasma concentration, the area under the plasma concentration/time curve (AUC) for up to 2 h after drug injection was smaller (2.2 times) in the leukemic rats than that for normals. Ho...

Soft-agar cloning was used to investigate possible granulopoietic-monopoietic regulatory defects in the chick with myeloblastic leukemia induced by avian myeloblastosis virus. The plasma levels of granulocyte-monocyte colony-stimulating ac tivity (CSA) of normal and leukemic plasmas were the same when undiluted or unfractionated plasmas were tested. How ever, dilution or fractionation revealed ...

Terminal deoxynucleotidyl transferase, an enzyme which catalyzes the polymerization of deoxyribonucleoside triphosphates, elongating oligo- or polydeoxynucleotide chains, but without direction from a nucleic acid template, is thought to be specific for thymus gland and thymus-derived cells. We have confirmed the observations that high levels are characteristic of thymus gland with both human an...