Blast cells, leukemic

O The acute leukemias are diseases of bone marrow resulting from aberrant proliferation of hematopoietic precursors. The hallmark of these malignancies is the leukemic blast cell, a visibly immature and abnormal cell in the peripheral blood that often replaces the bone marrow and interferes with normal hematopoiesis. These blast cells proliferate in the marrow and inhibit normal cellular elements, resulting in anemia, neutropenia, and thrombocytopenia. Leukemia also may infiltrate other organs, including the liver, spleen, bone, skin, lymph nodes, and central nervous system (CNS). Virtually anywhere there is blood flow, the potential for extramedullary (outside the bone marrow) leukemia exists. 

In addition to the cellular expression on malignant blast cells in AML, elevated levels of suPAR were found in plasma from leukemia patients [18]. In a longitudinal study, in which patients receiving chemotherapy were monitored, it was demonstrated that the suPAR level in plasma from patients with AML correlated with the number of circulating tumor cells and that these were reduced after chemotherapy. In plasma from AML patients, suPAR(II III) was detected in addition to intact suPAR. This is in contrast to findings in plasma from healthy individuals and from the ovarian cancer patients described above [144]. suPAR(II III) was also present in plasma made from bone marrow aspirates. The other cleaved form, uPAR(I), was only identified in urine. Lysates of the leukemic cells contained both intact uPAR and uPAR(II-III). The amounts of suPAR(II III) in plasma and uPAR(I) in urine were decreased following chemotherapy. In healthy controls, intact uPAR was detected in lysates from mononuclear cells in blood and suPAR(I-III) in plasma and bone marrow aspirates, while suPAR(II-III) was detected in urine [18]. 

Highly specific for thyroid carcinomas, with rare positivity in some leukemic blast cells... 

The tetrahydrofolate formylase was found in normal and leukemic leukocytes, the highest activities in immature blast cells of acute Leukemia (table 1). By determination of the 14C-formate incorporation a measurable netto de novo synthesis of purine nucleotides was only detected in immature leukemic cells. 

In figure 6 the influence of 6-MP and allopurinol on the tetrahydrofolate formylase in leukemic blast cells of 5 patients with acute leukemia is illustrated. 6-MP in a rather high concentration of 1.5 x 10 M has only a small inhibitory effect on this enzyme.By addition of allopurinol the inhibition of the enzyme by 6-MP was markedly increased, whereas allopurinol alone had no effect. This is explained by the fact, that allopurinol, by inhibition of the xanthine oxidase, reduces the inactivation of 6-MP to 6-thiouric acid. 

Effect of 6-MP on purine-phosphoribosy1-transferase in cell-free extract of leukemic blast cells. 

Activity of the formate activating enzyme in leukemic blast cells of 5 patients with acute leukemia under the action of 6-MP and allopurinol... 

When interpreting these results, it should be taken into consideration that RBC 6-TGN levels can act only as a surrogate marker for the situation in the leukemic blast and may not ideally reflect incorporation of 6-TGN into the DNA and RNA of target cells. This process is likely to be influenced by other thiopurine metabolites such as 6-MMPR and their effects on incorporation and cytotoxicity through inhibition of de novo purine synthesis (101,103). 

The uPAR expression on leukemic cells was compared to that on peripheral blood and bone marrow cells from healthy individuals in two studies using flow cytometric analysis. Both studies used the domain I-specific anti-Mo3f (also termed 3B10) and VIM-5 mAbs [147, 148], The uPAR expression on neutrophils and monocytes in peripheral blood from healthy donors was verified in both studies and found uPAR expressed neither on resting B nor on resting T lymphocytes. uPAR expressed on monocytes and neutrophils could bind the added ATF of uPA [147], showing that at least some of the uPAR molecules present on these cells were unoccupied. When blasts from AML patients were analyzed, they were found to express uPAR and the... 

Recombinant humanized IgG4 kappa monoclonal antibody conjugated with calicheamicin chemotherapy agent, binds to CD33 on leukemic blasts and immature normal cells of... 

In addition to the four bands of acid phosphatase isoenzyme activity in normal leukocytes, two other isoenzymes may appear in leukemia. In a case of acute granulocytic leukemia with 100% blast forms, only one electrophoretic band of activity was manifest this migrated between normal band 3 and 4 and was therefore designated 3b. In a case of leukemic reticuloendotheliosis with 98% reticulum cells, only one, and this a strongly staining band, was present this migrated anodically beyond No. 4 and was therefore designated No. 5 (L8). 

Although reversible increases in circulating blasts during GM-CSF treatment are sometimes noted and have raised concern on the possible accelerated occurrence of acute leukemia, the progression of myelodysplastic syndromes to acute myeloid leukemia has been only anecdotally reported (SEDA-19, 342) (57). There was no evidence of significant leukemic cell proliferation in patients with acute myeloid leukemia, and no increased... 

The fluorescence distribution of the cells is determined on a flow cytometer for rhodamine 123 in the FL1 channel and for daunorubicin in the FL2 channel. Preferably, identical detector settings are used every day. The blanks are used to position the signal in the first decade. The leukemic blast population is selected based on scatter characteristics. 

The leukemias are heterogeneous hematologic malignancies characterized by unregulated proliferation of the blood-forming cells of the bone marrow. These immature proliferating leukemia cells (blasts) physically crowd out or inhibit normal cellular maturation in bone marrow, resulting in anemia, neutropenia, and thrombocytopenia. Leukemic blasts may also infiltrate a variety of tissues such as lymph nodes, skin, liver, spleen, kidney, testes, and the central nervous system. 

Imatinib is a protein-tyrosine-kinase inhibitor. Imatinib inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome-positive (Ph-r) chronic myeloid leukemia (CML). Imatinib inhibits tumor growth of BCR-ABL transfected murine myeloid cells and BCR-ABL positive leukemia lines derived from CML patients in blast crisis. It also inhibits the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. It is indicated in the treatment of newly diagnosed adult patients with Ph-t CML in chronic phase patients with Ph-t CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha treatment children with Ph-t chronic phase CML whose disease has recurred after stem cell transplant or who are resistant to interferon-alpha therapy and treatment of gastrointestinal stromal tumors (GIST). 

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