Blast cells

AB is a 40-year-old white woman who went to urgent care because she hasn t been feeling well for a couple of days and has a fever. Her white blood cell (WBC) count results are greater than 100 X 109/L (100 X 103/jxl) with greater than 85% blast cells, which is indicative of acute leukemia. AB is admitted directly to the hospital to start chemotherapy. 

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. 

The DNA content of blast cells, hyper-, hypo-, or diploid, corresponding to increased, decreased, or normal chromosome numbers, has been considered prognostic. Lower-risk patients with hyperdiploidy (greater than 50 chromosomes) generally are between the ages of 1 and 9 years, whereas the higher-risk patients with normal diploidy (50 chromosomes) generally are older. 

By replacing the glass dewar with a stainless steel vessel, reactions can be studied that generate pressure. Such equipment needs to be placed in a blast cell where it can be operated remotely. Placing the dewar in an oven whose temperature is controlled to follow that in the reaction mass allows the study of the reaction under near adiabatic conditions. 

In an alternative scenario, 7-mer or 20-mer oligolysine sequences (which interact with heparan sulfate) have been fused to the C terminus of the fiber protein. This modification led to a dramatically increased and CAR-independent transduction of endothelial cells, smooth muscle cells, and macrophages in vitro and in vivo (up to > 100-fold) [33, 34], of myeloma cells and AML blast cells in vitro [35, 36], and of cultured glioma cells in vitro [37, 38], A similar approach has been used to fuse an RGD peptide (RDG-4C) to the C terminus of the fiber, which led to an increased transduction of endothelial cells in vitro and in vivo [33, 39], The same RGD-containing peptide has also been incorporated into the HI-loop of the fiber protein, resulting in an up to 1000-fold increased and CAR-independent transduction of primary endothelial cells and ovarian and head and neck cancer cells in vitro [40, 41]. 

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]. 

In acute myeloid leukaemia or lymphatic leukaemia as well as in acute leukaemic episodes in non-Hodgkin lymphoma, involvement of the liver may only be detectable clinically by the presence of hepatomegaly and subicterus. Laboratory parameters usually show slightly elevated transaminase as well as bilirubin values, and distinct cholestasis is occasionally observed. (7) Acute hepatic failure can occur during the course of acute leukaemia, (l, 8,26,65) Histologically, there are massive, yet uniform blast-cell infiltrates these are found mainly within the portal fields in acute lymphatic leukaemia (about 95%) and within the sinusoids in acute myeloid leukaemia (about 75%). Involvement of the liver is of no consequence with regard to the underlying disease and its therapy. Secondary infections require systemic treatment with antibiotics and/or antimycotics. 

In one study, severe erythroderma and a dramatic proliferation of blast cells after each dose of hM-CSF were the only significant severe adverse effects, reported in one patient each (SEDA-19, 345). 

Vandermeulen, J.H., 1975. Studies on reef corals. III. Fine structural changes of calico-blast cells in Pocillopora damicornis during settling and calcification. Mar. Biol., 31 69—77. 

Nooter, K., Sonneveld, P., Oostrurn, R., Herweijer, H., Hagenbeek, T., and Valerio, D. (1990) Overexpression of the mdrl gene in blast cells from patients with acute myelocytic leukemia is associated with decreased anthracycline accumulation that can be restored by cyclosporin-A. Int. J. Cancer 45, 263-268. 

---