Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4+CD8+ double-positive (DP) phenotype is seen in a few cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a matter of controversy. To address this issue, we studied phenotypical features in eight cases of DP T cell leukemia. Thymic DP T cells and peripheral CD8+ T cells have CD8 of alphabeta subunit, while CD8alphaalpha is induced in CD4+ T cells on activation with IL-4. We found that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim expression of CD8alphaalpha, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high levels of IL-4. These findings suggest that they may be derived from peripheral CD4+ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed CD8alphaalpha, suggestive of an activated peripheral T cell origin. One case expressed CD8alphaalpha dim and IL-4 mRNA, while the other two cases expressed no IL-4 mRNA and showed CD8alphaalpha bright phenotype, features not found in normal T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL) expressed CD8alphabeta. The DP phenotype is relatively common in T-PLL, and CD4+CD8alphabeta+ is characteristic of thymic T cells. The DP T-PLL cells did not express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down-regulated at the late stage of thymic T cell development. On the basis of these findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.
Leukemia 1998 Apr
PMID:Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia. 955 7

This study reports findings from a retrospective, comprehensive review of 80 cases of adult AML in regard to cytomorphology, enzyme cytochemistry (EC), flow cytometric immunophenotyping (FCI), and chromosomal analysis. From this review, we conclude that diagnostically challenging cases can only be subtyped by combining the cytomorphology with EC, FCI, and subsequent cytogenetic results. This is particularly true in recognizing the hypogranular variant of AML,M3 (AML, M3m) and distinguishing it from other subtypes. Nonlineage expression of markers (CD1, CD2, CD4, CD5, CD7, and CD56) was nonspecific as to AML subtype. Of interest, CD2 coexpression in acute myelomonocytic leukemia with eosinophilia (M4-Eo) was exclusively associated with inversion of chromosome 16 (inv 16) and was not observed in the other M4-Eo's without inv16. We also recognized a previously undescribed M3m with CD56 coexpression, heightening awareness of this entity which needs to be distinguished from the unique subtype of CD56+ AML with otherwise similar immunophenotypic and morphologic characteristics. In addition, nonlineage expression of CD19 alone was exclusively associated with the cytogenetic finding of t (8;21) (q22; q22) and thus may represent a favorable prognostic indicator by FCI.
 ...
PMID:Comprehensive review of adult acute myelogenous leukemia: cytomorphological, enzyme cytochemical, flow cytometric immunophenotypic, and cytogenetic findings. 1002 33

Thirty T cell receptor (TCR)gammadelta+ T cell acute lymphoblastic leukemias (T-ALL) were analyzed for their immunophenotype, as well as for the rearrangements and junctional regions of the TCRG and TCRD genes. In 15 cases membrane expression of TCRgammadelta proteins could be studied extensively by flow cytometry with a new Vgamma/Vdelta antibody panel. Virtually all TCRgammadelta+ T-ALLs expressed TdT, CD2, CD3, CD5, CD6, and CD7, but they were heterogeneous in their CD1/CD4/CD8 immunophenotype. The majority expressed either CD4+/CD8- or CD4+/CD8+, whereas only 7/30 TCRgammadelta+ T-ALLs lacked both antigens. Despite heterogeneity in the rearranged TCRG and TCRD genes, we found preferential protein expression of VgammaI (21/30), Jgamma2.3 (19/30) and Cgamma2 (21/30) gene products in the TCRgammadelta+ T-ALL. Expressed TCRD genes were largely limited to Vdelta1-Jdelta1, except for six patients who expressed non-Vdelta1 TCRdelta chains (Vdelta2-Jdelta1, Vdelta2-Jdelta3, Vdelta3-Jdelta1, Vdelta6-Jdelta2, and two Valpha-Jdelta1). In spite of the relatively limited combinatorial repertoire of the TCRG and TCRD genes, the junctional region diversity of the expressed genes was extensive. The Vgamma/Vdelta antibody panel confirmed the predominant, but not exclusive, expression of VgammaI and Vdelta1 proteins. Importantly, not a single T-ALL expressed the common peripheral blood Vgamma9+/Vdelta2+ phenotype. These immunogenotypic and immunophenotypic characteristics represent excellent targets for flow cytometric and PCR-based detection of 'minimal residual disease' in all TCRgammadelta+ T-ALL. Comparison of non-Vdelta1+ TCRgammadelta T-ALLs with the more common Vdelta1+ type showed a trend towards a more mature immunogenotype in the former. Firstly, more complete TCRD rearrangements were identified on the non-expressed allele in the non-Vdelta1+ group (83% vs 43%); secondly, a higher frequency of 'end-stage' Jgamma2.3 gene rearrangements was found in non-Vdelta1 cases on both TCRG alleles (83% vs 66%); thirdly, a higher frequency of complete TCRB rearrangements was found in non-Vdelta1 cases (79% vs 50%).
Leukemia 1999 Feb
PMID:Immunophenotypic and immunogenotypic characteristics of TCRgammadelta+ T cell acute lymphoblastic leukemia. 1002 94

A 58-year-old man was referred to our hospital because of painful swelling in the left lower leg and leukocytosis in January 1999. Moderate hepatosplenomegaly but no lymph node swelling was observed. Marked leukocytosis (leukocytes 44.9 x 10(4)/microliter with 95% morphologically prolymphocytes) and thrombocytopenia were detected. The surface phenotype of the leukemia cells was CD1-2+3+5+7+4+8+25+. Magnetic resonance imaging revealed dilated veins in the left lower leg. An abnormal 47XY, +22 karyotype was detected in 1/20 cells. Tests for HTLV-I antibody were negative. A diagnosis of T-cell prolymphocytic leukemia (T-PLL) was made on the basis of data including cytochemical and electron microscopic findings. Although 2 courses of chemotherapy comprising vincristine, cyclophosphamide, and prednisolone improved the venous thrombosis in the leg, the leukemia cells were refractory to chemotherapy. To prevent the recurrence of venous thrombosis due to leukostasis, the patient underwent repeated leukapheresis. The leukocyte count was maintained at around 20.0 x 10(4)/microliter after total 7 courses of leukapheresis, one course of which comprised 7l of extracorporeal circulation. In addition to the rare presentation of venous thrombosis, the CD4+8+25+ phenotype observed in this case is rare in patients with T-PLL.
 ...
PMID:[T-cell prolymphocytic leukemia with CD4+8+25+ phenotype in a patient presenting with venous thrombosis in the lower leg]. 1062 30

The process of terminal differentiation is associated with exit from the cell cycle and loss of the proliferative potential of cells. The cyclin-dependent kinase inhibitors (CDIs) play critical roles in check-point functions during the cell cycle and as inhibitors of cell proliferation. Loss of their activities can impair development and differentiation and contribute to the uncontrolled proliferation characteristic of cancer cells. When the promyelocytic leukemia cell line HL60 is induced to differentiate in vitro, by a variety of agents, cellular levels of the CD1 proteins p21Cip1 and p27Kip1 are increased. To further address the roles of these two proteins in differentiation, we have overexpressed either a human p21Cip1 or p27Kip1 construct in HL60 cells. The overexpression of p21Cip1 accelerated both the monocytic and granulocytic differentiation of HL60 cells triggered by TPA or DMSO, respectively. The accelerated and more dramatic induction of differentiation seen in the p21Cip1 overexpressors was associated with a more rapid reduction of CDK2 kinase-associated activity, increased levels and more rapid dephosphorylation of the Rb protein, and increased levels of the cyclin D3 protein. Stable overexpression of p27Kip1 also enhanced TPA-induced differentiation of HL60 cells. These studies provide direct evidence that the increased expression of p21Cip1 and p27Kip1 play a causal role in the process of terminal differentiation of HL60 cells. Therefore, agents that enhance the expression of one or both of these proteins might be useful in therapy by enhancing the terminal differentiation of leukemia cells.
 ...
PMID:Overexpression of p21Cip1 or p27Kip1 in the promyelocytic leukemia cell line HL60 accelerates its lineage-specific differentiation. 1069 93

Malignancies involving natural killer (NK) cells are rare disorders. The complexity of NK cell-involving disorders has only recently been appreciated. Modern classifications discern immature (precursor) from mature NK cell leukemias-lymphomas. Continuous NK leukemia-lymphoma cell lines represent important model systems to study these neoplasms. While there are a number of putative NK cell lines which are, however, either not characterized, not immortalized, non-malignant, non-NK, or plain false cell lines, six bona fide malignant NK cell lines have been established and are sufficiently well characterized: HANK1, KHYG-1, NK-92, NKL, NK-YS and YT. Except for YT which was derived from a not further defined acute lymphoblastic lymphoma, these cell lines were established from patients with various NK cell malignancies. Five of the six cell lines are constitutively interleukin-2-dependent. Their immunoprofile is remarkably similar: CD1-, CD2+, surface CD3 (but cytoplasmic CD3epsilon+), CD4-, CD5-, CD7+, CD8-, CD16-, CD56+, CD57-, TCRalphabeta-, TCRgammadelta-, negative for B cell and myelomonocytic markers. The immunoglobulin heavy chain and T cell receptor genes are all in germline configuration. All six lines show complex chromosomal alterations, with both numerical and structural aberrations, attesting to their malignant and monoclonal nature. Functionally, these cells which contain azurophilic granules in their cytoplasm are nearly universally positive in NK activity assays. Three of five cell lines are Epstein-Barr virus-positive (type II latency). The composite data on these six cell lines allow for the operational definition of a typical malignant NK cell line profile. NK leukemia-lymphoma cell lines will prove invaluable for studies of normal and malignant NK cell biology.
Leukemia 2000 May
PMID:Malignant hematopoietic cell lines: in vitro models for the study of natural killer cell leukemia-lymphoma. 1080 5

We present the establishment of a natural killer (NK) leukemia cell line, designated KHYG-1, from the blood of a patient with aggressive NK leukemia, which both possessed the same p53 point mutation. The immunophenotype of the primary leukemia cells was CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16+, CD56+, CD57+ and HLA-DR+. A new cell line (KHYG-1) was established by culturing peripheral leukemia cells with 100 units of recombinant interleukin (IL)-2. The KHYG-1 cells showed LGL morphology with a large nucleus, coarse chromatin, conspicuous nucleoli, and abundant basophilic cytoplasm with many azurophilic granules. The immunophenotype of KHYG-1 cells was CD1-, CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16-, CD25-, CD33+, CD34-, CD56+, CD57-, CD122+, CD132+, and TdT-. Southern blot analysis of these cells revealed a normal germline configuration for the beta, delta, and gamma chains of the T cell receptor and the immunoglobulin heavy-chain genes. Moreover, the KHYG-1 cells displayed NK cell activity and IL-2-dependent proliferation in vitro, suggesting that they are of NK cell origin. Epstein-Barr virus (EBV) DNA was not detected in KHYG-1 cells by Southern blot analysis with a terminal repeat probe from an EBV genome. A point mutation in exon 7 of the p53 gene was detected in the KHYG-1 cells by PCR/SSCP analysis, and direct sequencing revealed the conversion of C to T at nucleotide 877 in codon 248. The primary leukemia cells also carried the same point mutation. Although the precise role of the p53 point mutation in leukemogenesis remains to be clarified, the establishment of an NK leukemia cell line with a p53 point mutation could be valuable in the study of leukemogenesis.
Leukemia 2000 May
PMID:A novel natural killer cell line (KHYG-1) from a patient with aggressive natural killer cell leukemia carrying a p53 point mutation. 1080 26

Methyl-tertiary-butyl-ether (MTBE) was introduced into motor fuels in 1992 to reduce carbon monoxide automotive emissions in areas where the National Ambient Air Quality Standards for CO were exceeded. At a meeting of the National Toxicology Program's Board of Scientific Counselors (2-3 December 1998), data were presented showing that exposure to MTBE caused increased incidence of liver tumors, renal adenomas, carcinomas and interstitial cell adenomas of the testes in male, and lymphomas and leukemia in female CD1 mice [National Toxicology Program, 1998]. Despite this evidence, the NTP Board defeated a motion to list MTBE as "Reasonably anticipated to be a human carcinogen" by a vote of 6 to 5. This decision directly contravenes rules and procedures previously established by NTP for assessing carcinogenicity of chemical compounds. Good public health policy dictates that the NTP Board conduct another review of MTBE with proper consideration of the criteria that have been established for listing agents as carcinogens. Millions of Americans who are exposed daily to this chemical deserve an unbiased evaluation of carcinogenic agents being introduced into the environment.
 ...
PMID:Methyl-tertiary-butyl-ether (MTBE) misclassified. 1133 14

The immunophenotypic features of leukemia blast cells were analyzed in a group of 156 patients with different immunological subtypes of acute leukemia, both lymphoblastic and myeloblastic. Of the 58 patients for whom immunologic studies were performed at relapse, 42 (72%) showed changes in the expression of immunologic markers. The minor shifts in B-ALL were observed most frequently and concerned of the loss of CD34 antigen in 17 cases and the loss of cALLA (CD10) in 7 cases of B-ALL at the first relapse. The acquisition of cell markers was not frequently observed, only in four cases could be seen. HLA-DR molecules remained relatively constant from diagnosis to relapse. In 2 from 3 T-ALL cases the loss of CD1 and CD2 markers, respectively, was noticed at relapse. CD5 and CD7 markers were relatively stable. In AML cases at relapse the acquisition of CD13 marker (in 4 from 7 cases) was often observed. It was interesting that comparing to the B-ALL cases, the loss of CD34 marker in AML cases was stray. In one case the acquisition of this antigen at relapse was actually observed. The major interlineage shift was detected in one case of B-ALL, that was newly diagnosed at relapse as AML M4 and presented different cytogenetic features. This case provides strong connection with the treatment, as more recently epipodophyllotoxins (vumon in our patient) have been linked to the development of secondary AML associated with a shorter latency period. The immunophenotypic changes frequently occur at relapse in all acute leukemia types. The shifts (loss or acquisition) in expression of individual markers at relapse are bound with the first diagnosis and may have a relationship to the treatment and are important for correct assessment of minimal residual disease.
 ...
PMID:Shifts in expression of immunological cell markers in relapsed acute leukemia. 1158 83

In our study we described the immunophenotypic characteristics of an ectopic thymus found in an eight month old male baby. Comparing with the results of normal thymic cells we did not found any difference or abnormalities in the phenotype. A brief discussion of theories of histogenesis and possible differential diagnosis of ectopic thymus is included. The most common immune pattern of both, ectopic and normal thymuses, was expression of TdT,CD7,cCD3,CD1 and dual CD4/CD8. Early results of immunological examination confirmed by histopathology stated the diagnosis of ectopic thymus and excluded other causes (infection, trauma, neoplasm and congenital abnormalities). The study of both, ectopic and normal thymic tissue provides a perfect model for comparative analysis of some T-acute lymphoblastic leukemia (T-ALL). Both, thymocytes and some cases of our T-ALL (20 of 48 examined T-ALL) had a specific late cortical T-cell phenotype. We observed new qualities of both, thymic cells and T-ALL cells of a late cortical phenotype that resulted in cell populations localized in the so-called "empty spaces", in fluorescence histograms, that might be discriminated from internal T-cell populations with normal antigen expression. An important sign of T-ALL in common is to display aberrant marker combinations and the tendency to drop specific normal T-cell antigens. Aberrant markers were present in our study in a phenotypic group of a late cortical T-ALL in 11 cases (55.0%) of the 20 studied. As aberrant markers we observed mostly CD10, CD34, HLA-DR and CD13. Furthermore, the tendency to drop specific normal T-cell markers could be recognized in one case of a late cortical T-ALL in the form of TCRab and TCRgd absence. DNA analysis did not reveal any changes in proliferation index either in thymocytes (normal or ectopic), or in T-ALL of a late cortical T-cell phenotype. Based on our findings the clinical utility of comparing the results obtained from the immunophenotypic characterization of healthy hematopoietic and leukemia cells can be concluded. An exact and early diagnosis of hematopoietic disorders (ectopic thymus, T-ALL and T-NHL) and identification of identical phenotypic patterns at different times (for more exact minimal residual disease detection during and after therapy) could be obtained.
 ...
PMID:The analogy in cell immunophenotype and parameters of cell cycle of ectopic thymus, normal thymus, and some acute lymphoblastic leukemia of T-phenotype. 1245 29


<< Previous 1 2 3 4 5 6 7 Next >>