Hematologic pathology最新文献

Drug resistance is a critical problem in the therapy of hematologic malignancies. Recent advances in the transplantation of human normal and transformed hematopoietic cells into severe combined immunodeficient (SCID) mice provide an opportunity to study the biologic and molecular events that mediate resistance. We studied the engraftment of several human myelogenous leukemia cell lines sensitive and resistant to amsacrine (mAMSA), vincristine, hycamptamine, methotrexate, or doxorubicine (KBM3/AMSA, K562/Vcr, HL60/Hy10, K562/MTX, HL60/Dox). The distribution and growth potential of these cells was evaluated using molecular and histologic techniques. Inoculation of 2 x 10(7) leukemic cells led to manifestation of disease, and subsequent tissue analysis showed evidence of leukemia. The survival of mice varied from 21 to 135 days. Terminally, the animals showed symptoms of wasting, development of local tumors, or both. Massive leukemic dissemination with infiltration of bone marrow and various organs including lungs, spleen, liver, ovaries, and brain was detected in most cases. No differences were observed in the tissue distribution of sensitive as compared to resistant leukemia cells. These findings demonstrated that human leukemic cells retain, in SCID mice, the clinico-pathologic picture of the original disease in humans. The development of numerous drug-resistant phenotypes in vitro does not alter the subsequent behavior of resistant cells in vivo when compared with sensitive counterparts. The levels of resistance are not modified by passage through SCID mice. This model offers an opportunity for developing new preclinical in vivo systems for modulation of drug resistance, and the combination of this in vivo model with gene transfer methods will also provide an important system for testing the molecular alterations involved in drug resistance and leukemic progression.

Graft thrombotic occlusion is a common complication in patients undergoing aorto-coronary bypass surgery. Clotting activation seems to contribute to the thrombotic event. We have determined the plasma concentrations of two hemostatic markers, thrombin-antithrombin (TAT) complexes and prothrombin fragment 1+2 (F 1+2) in 100 patients undergoing revascularization procedures of whom 81 underwent shunt angiography. Angiographically proven graft occlusion was present in 19 patients (23.5%). A significant increase of both parameters was observed immediately after surgery and on postoperative days 1 and 5 (p < 0.001), although a relationship to graft occlusion could not be demonstrated. However, the preoperative TAT concentration was higher in patients developing graft occlusion (p < 0.01). We conclude that there is a marked clotting activation in patients undergoing aorto-coronary bypass surgery, as demonstrated by elevated TAT and F 1+2 concentrations. Preoperative TAT values can be good markers of early graft occlusion.

The purpose of the study was to analyze the clinical and laboratory characteristics of patients with acute lymphocytic leukemia (ALL) who exhibited myeloperoxidase-positive blasts by electron microscopy (EM-MPO-positive), and assess their response to therapy and their prognosis. Since 1988, 21 adults with newly-diagnosed ALL and EM-MPO-positive blasts were referred to our service. In addition to documentation of their clinical and hematopathologic characteristics, patients underwent cytogenetic, immunophenotypic, molecular, and electron-microscopic evaluations. Twenty patients were treated with the vincristine-Adriamycin-dexamethasone (VAD) regimen, and one patient was induced with amsacrine and high-dose cytosine arabinoside (ara-C). The 21 patients were among 141 patients with ALL (15%) seen during the same period. Their median age was 46 years (range 15 to 77 years). The immunophenotype was T-cell ALL in 12 patients (57%). Karyotypic studies did not demonstrate specific recurrent abnormalities. The median percentage of EM-MPO-positive blasts was 15% (range 3% to 45%). Eighteen patients (85%) had high-risk ALL. With induction chemotherapy 15 of 20 (75%) receiving VAD therapy achieved a complete remission (CR). However, the median CR duration was 18 months, and the median survival was 18 months with a 3-year disease-free survival rate of 25%. There were eight relapses and one lineage switch to acute myelogenous leukemia (AML). Patients with ALL and EM-MPO-positive disease are a unique subgroup with long-term poor prognosis on conventional anti-ALL therapy, and may benefit from intensification treatments with agents effective against AML.

We studied the effect of dibutyryl cyclic adenosine-3',5'-monophosphate (dbcAMP) and several cytokines on the expression of IgG Fc receptor subclasses (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) and low-affinity IgE Fc receptors (Fc epsilon RII/CD23) on peripheral eosinophils and on eosinophils differentiated in vitro from cord blood mononuclear cells by interleukin 5 (IL-5). These eosinophils expressed Fc gamma RII, and few, if any, Fc gamma RI and Fc gamma RIII as determined by flow cytometry with specific monoclonal antibodies. dbcAMP enhanced the Fc gamma RII expression, but did not induce the Fc gamma RI and Fc gamma RIII expression. Interferon-gamma (IFN-gamma) enhanced Fc gamma RII expression at the same degree as did dbcAMP. IFN-gamma also induced Fc gamma RIII expression on peripheral eosinophils but not on eosinophils grown in the presence of IL-5. Eosinophils grown in the presence of IL-5 showed a relatively immature phenotype, determined by electron microscopy and the low content of eosinophil cationic protein. Contrary to its enhancing effect on Fc gamma RII expression, dbcAMP suppressed the IFN-gamma-induced Fc gamma RIII expression on peripheral eosinophils. Other cytokines examined did not show any effects on Fc gamma R expression. Fc epsilon RII/CD23 expression was neither detected nor induced. These results indicate that expression of Fc gamma RII and Fc gamma RIII on eosinophils is regulated differently and that cAMP and IFN-gamma play important roles in the regulation of Fc gamma R expression.

T cells play a central role in the immune system as effectors and regulators. They become activated upon antigen recognition by their T-cell receptors (TCR). The TCR repertoire is established by developmentally regulated TCR gene rearrangements and shaped by predominantly intrathymic selection processes. Failure of this system can lead to autoimmune disease. TCR gene probes and primers are widely used to distinguish polyclonal from abnormal clonal T-cell proliferations in Southern blot or polymerase chain reaction (PCR) procedures. T cells are normally activated by signal transduction through the TCR/CD3 complex and accessory molecules such as CD4 and CD8. Protein tyrosine kinases (PTKs) and nuclear transcription factors (TFs) are important intracellular signaling molecules. Chromosomal abnormalities in T-cell leukemia often affect the gene loci of TFs, PTKs, and sometimes other growth regulatory proteins. Aberrant activation of these molecules may lead to alteration of the signaling cascade and interference with ordered T-cell development and differentiation. The increasing knowledge about different functional aspects of TCR physiology thus contributes to the diagnosis and understanding of reactive and malignant T-cell disorders. This will eventually lead to new diagnostic concepts and novel therapeutic strategies.

To assess the reliability of DNA estimation using image cytometry, deparaffinized lymph nodes from 70 patients with Hodgkin's disease were examined and the results obtained were compared with those from flow cytometry. Image analysis without discriminating between the various cell types, as found in Hodgkin's disease, revealed no separate aneuploid peak. Selecting on morphologically defined nuclear types DNA aneuploidy was detected in 20% of the cases (14/70). The aneuploid populations were limited to the population of nuclei defined as Reed-Sternberg (RS)-like or medium-sized lymphocytes. Benign lymph nodes DNA aneuploidy was not found in any of the controls. Comparison of DNA histograms obtained by image and flow cytometry showed aneuploid peaks using image cytometry in 4 of 30 diploid and 10 of 40 aneuploid flow histograms. In conclusion, image analysis using the CAS 200 system as compared to flow cytometry is more time-consuming and less sensitive to assess ploidy status, although it may provide extra information in some selected cases. Evidence is obtained that DNA aneuploidy in Hodgkin's disease is preferentially expressed by cells with the RS/H-like and medium-sized lymphocyte morphology.

The expression of CD34 antigen on the surface of bone marrow cells during remission induction was studied in 27 selected acute lymphoblastic leukemia (ALL) patients who were CD34 negative at presentation and were stratified to receive high-dose methylprednisolone (30 mg/kg/day po) or conventional-dose prednisolone (2 mg/kg/day po). Patients received either induction with L-Asparaginase, vincristine (VCR), and high-dose methylprednisolone [HDMP, 30 mg/kg/day po for 1 week, 20 mg/kg/day po for 1 week, and 20 mg/kg/day po every other day for 2 more weeks (20 patients)], or identical induction in which HDMP was replaced by prednisolone 2 mg/kg/day by mouth for 4 weeks (8 patients). Bone marrow cells from all patients were studied 1,2, and 4 weeks after initiation of treatment for expression of the CD34 antigen using a three-step indirect immunoperoxidase staining technique. In the 20 patients with ALL who received HDMP the percentage of normal bone marrow cells expressing CD34 was significantly higher (p < 0.05) than in the 8 patients who did not receive HDMP. The mean percentage of CD34-positive bone marrow cells during the fourth week was 17.2% in patients with ALL who received HDMP, whereas patients who received 2 mg/kg prednisolone per day had only 6.1% CD34 cells in the marrow. Absolute polymorphonuclear leukocyte (pmnl) count was also significantly higher in the patients who received HDMP in the second and third week of therapy [(absolute pmnl count was 2197.7/mm3 in the second week and 4091.8/mm3 in the fourth week in the patients who received HDMP compared to 974.4/mm3 and 1556.5/mm3 in the patients who did not receive HDMP) (p < 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are differentiated B-cell leukemias with well-described clinical, morphologic, and immunologic characteristics. We encountered two patients with indolent chronic B-cell leukemia showing overlapping features of these malignancies. The patients had progressive splenomegaly, minimal lymphadenopathy, and abnormal lymphoid cells with abundant cytoplasm and villi, which were strongly positive for surface antigens CD22 and CD11c, features associated with HCL. However, blood counts showed lymphocytosis without neutropenia and monocytopenia, and the bone marrow biopsies demonstrated tightly aggregated nodules of lymphocytes. In addition, the lymphoid cells were dual positive for CD19 and CD5, displaying weak-to-moderately positive monoclonal surface immunoglobulin, findings strongly suggestive of CLL. One patient failed to respond to therapy with chlorambucil and prednisone. The second patient showed a partial response to treatment with 2-chlorodeoxyadenosine. We compare our patients with similar variants of differentiated B-cell leukemias reported in the literature, including disorders described as hairy cell variant (HCL-V) or splenic lymphoma with villous lymphocytes (SLVL).

Non-Hodgkin's lymphomas have been recognized as an important and frequently fatal part of the spectrum of diseases associated with HIV infection. These are most often high-grade B-cell lymphomas usually of immunoblastic and small cell non-cleaved subtypes. Sporadic reports of T-cell lymphomas associated with HIV infection are found in the literature. Two have been reported to be CD30 positive presenting with lymph node and skin involvement. We report a case of an AIDS patient with a T-cell anaplastic large-cell lymphoma that was CD30-positive and presented in bone. This is most probably a sporadic event rather than another part of the AIDS-associated spectrum of disease.