lewis-x-antigen and Leukemia--Monocytic--Acute

Resting human NK cells require a two-stage activation process that we have previously described as "priming" and "triggering." NK-sensitive tumor cells provide both priming and triggering signals. NK-resistant tumors evade lysis, mostly by failure to prime; however, we recently reported a tumor cell line (CTV-1) that primes resting NK cells but fails to trigger lysis. In this article, we report two additional leukemia cell lines that prime NK cells but are resistant to lysis. Tumor-mediated NK priming is via CD2 binding to a ligand within CD15 on the tumor cell. NK-resistant RAJI cells became susceptible to NK lysis following transfection and expression of CD15. Blockade of CD15 on K562 cells or on CD15(+) RAJI cells significantly inhibited lysis, as did blockade of CD2 on resting NK cells. NK priming via CD2 induced CD16 shedding, releasing CD3ζ to the CD2, leading to its phosphorylation and the subsequent phosphorylation of linker for activation of T cells and STAT-5 and synthesis of IFN-γ. Blockade of C-type lectin receptors significantly suppressed the tumor-mediated priming of NK cells, whereas blockade of Ig-superfamily-like receptors had no effect at the NK-priming stage. Tumor priming of resting NK cells was irrespective of HLA expression, and blockade of HLA-killer Ig-like receptor interactions did not influence the incidence or degree of priming. However, CD15-CD2 interactions were critical for NK priming and were required, even in the absence of HLA-mediated NK inhibition. Tumor-mediated priming led to a sustained primed state, and the activated NK cells retained the ability to lyse NK-resistant tumors, even after cryopreservation.

Topics: CD2 Antigens; Cell Differentiation; Cell Line, Tumor; Cell Lineage; Coculture Techniques; Cytotoxicity, Immunologic; Disease Resistance; Fucosyltransferases; Humans; Killer Cells, Natural; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Lewis X Antigen; Ligands; Lymphocyte Activation; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Binding; Receptors, KIR; Resting Phase, Cell Cycle; Signal Transduction

To study the clinicopathologic features, diagnosis and differential diagnosis of extramedullary infiltration of acute monocytic leukemia/monoblastic sarcoma.. Five cases of extramedullary infiltration of acute monocytic leukemia/monoblastic sarcoma were selected from 102 cases of myeloid sarcoma diagnosed during the period from 1990 to 2006. The clinicopathologic findings and followup data were retrospectively analyzed. Immunohistochemical study was also carried out with SP method.. Among the 5 cases studied, 3 were males and 2 were females, including 2 children and 3 adults. Generalized lymphadenopathy was found in 4 patients and skin lesions were observed in 2 patients. The tumor cells in all cases were positive for CD68 (KP1), CD68 (PGM1), lysozyme and CD45. They were negative for MPO, CD15, CD163, TdT, CD117, T and B cell markers. The Ki-67 index ranged from 40% to 80%. Follow-up data were available in all the 5 patients. Four of the 5 patients died of the disease, with the average survival time being 6.25 months.. Monoblastic sarcoma is a rare disease with poor prognosis. It is almost impossible to distinguish monoblastic sarcoma from granulocytic sarcoma and other types of small round cell tumors on the basis of morphologic examination alone. Immunohistochemistry is mandatory for a correct diagnosis.

Topics: Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Child; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Immunophenotyping; Leukemia, Monocytic, Acute; Leukocyte Common Antigens; Lewis X Antigen; Male; Receptors, Cell Surface; Sarcoma; Sarcoma, Myeloid

The abnormality in the translocation of chromosomes 4 and 11 (t[4;11]) has been characteristically associated with calla-negative CD15(+) acute lymphoblastic leukemia (ALL) of early pre-B-cell origin. Transformation of a lymphoblastoid to a monoblastoid morphologic structure has rarely been described at relapse in these cases; however, these cases have lacked flow cytometric immunophenotyping (FCI) and genotypic studies (GS) to define the immunophenotype of and the presence of a B-cell gene rearrangement in the monoblastoid component. We report a case of CD15(+), CD10(-) ALL of early pre-B-cell origin defined by morphologic testing and FCI with the t(4;11) abnormality. At relapse, the morphologic testing, enzyme cytochemistry, and FCI data were characteristic of monoblastic leukemia. The t(4;11) abnormality persisted with associated additional chromosomal abnormalities, and the monoblasts contained a B-cell gene rearrangement by GS. These findings support the concept that both processes arose from a multipotential progenitor cell.

Topics: Antigens, CD; B-Lymphocytes; Blast Crisis; Bone Marrow Transplantation; Chromosome Mapping; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 4; Female; Flow Cytometry; Gene Rearrangement, B-Lymphocyte; Humans; Immunoglobulin Heavy Chains; Immunophenotyping; Leukemia, Monocytic, Acute; Lewis X Antigen; Middle Aged; Neoplasms, Second Primary; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Translocation, Genetic