Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case is reported of a 62-yr-old male suffering from chronic myelogenous leukemia (CML) who developed an extramedullary, para-orthic lymph-nodal blast crisis without blood or bone marrow involvement and expression of CD56/NK associated marker. The diagnosis was performed on ultrasound-guided fine-needle cytology by an immunocytochemical and flow cytometric analysis. Conventional smears showed a monomorphous population of disperse, undifferentiated cells without cytoplasm. Cells showed fragile nuclei, vesicular chromatin, and evident nucleoli. Immunocytochemistry performed on cytospin slides were negative for cytokeratin, LCA, CD20, CD45Ro, and myeloperoxidase (MPO). Flow cytometry analysis proved the myeloid origin of the tumor by expression of CD13, CD34, and CD38 and showed aberrant expression of CD56. Cytological diagnosis was confirmed by histological examination. CD56 expression is generally an expression of NK lymphoid proliferation and may be observed in acute myelogenous leukemia but has rarely been reported in CML and its related blast crisis. This unusual expression, its possible explanation, the related technical problems, and clinicopathological aspects are discussed.
 ...
PMID:Expression of NK-associated antigens in extramedullary lymph nodal blast crisis of chronic myeloid leukemia on fine-needle cytology. 1220 63

Knowledge of the blast phenotype in myelodysplastic syndrome (MDS) would be valuable, as in other malignancies, but remains sparse. This is mainly because MDS blasts are a minor population in clinical samples, making analysis difficult. Thus, for this blast phenotype study, we prepared blast-rich specimens (using a new density centrifugation reagent for harvesting blasts) from blood and marrow samples of 95 patients with various MDS subtypes and 21 patients with acute leukemia transformed from MDS (AL-MDS). Flow cytometry revealed that a high proportion of the enriched blast cells (EBCs) from almost all patients showed an immunophenotype of committed myeloid precursors (CD34(+)CD38(+)HLA-DR(+)CD13(+)CD33(+)), regardless of the disease subtype. The cytochemical reaction for myeloperoxidase was negative in 58% of the cases. Thus, the EBC phenotype is more immature in MDS than in de novo acute myeloid leukemia. MDS EBCs often coexpressed stem cell antigens and late-stage myeloid antigens asynchronously, but rarely expressed T- and B-lymphoid cell-specific antigens. Markers for myeloid cell maturation (CD10 and CD15) were more prevalent on EBCs from low-risk MDS (refractory anemia [RA] and RA with ringed sideroblasts), whereas markers for myeloid cell immaturity (CD7 and CD117) were more prevalent on EBCs from high-risk MDS (chronic myelomonocytic leukemia, RA with excess blasts [RAEB], and RAEB in transformation) and AL-MDS. A shift to a more immature phenotype of EBCs, accompanying disease progression, was also documented by sequential phenotyping of the same patients. Further, CD7 positivity of EBCs was an independent variable for a poor prognosis in MDS. These data represent new, valuable information regarding MDS.
 ...
PMID:Clinical significance of phenotypic features of blasts in patients with myelodysplastic syndrome. 1239 41

Immune-mediated elimination of tumor cells by donor T cells recognizing recipient minor H antigens contributes to the curative potential of allogeneic HCT. The importance of the allogeneic response to a successful outcome is clearly illustrated by the results of stem cell transplant for malignancy after nonmyeloablative conditioning. Remarkably little is understood about the molecular nature of minor H antigens and this has impeded efforts to determine the role of specific disparities in graft versus tumor reactions or to manipulate T cell responses to augment antitumor activity without exacerbating GVHD. The isolation of minor H antigen-specific CD8+ and CD4+ T cell clones from recipients of allogeneic HCT has provided the reagents to characterize their expression on leukemic progenitors and to identify the genes encoding these antigens. Using cDNA expression cloning, genetic polymorphisms in the human IFI-75, Uty, KIAA0020, and UGT2B17 genes have been identified to encode new minor H antigens presented by HLA A3, B8, A2, and A29 respectively. Two of these genes are preferentially expressed in hematopoietic cells including leukemic progenitors suggesting it may be possible to augment T cell responses to promote a selective graft versus leukemia effect. A third gene, UGT2B17 is highly expressed in liver and GI tract and may be a target for GVHD in these organs. The studies to identify the molecular nature of minor H antigens have provided insights into the complexities of the graft versus host response associated with allogeneic HCT, but the challenge for the future will be to develop strategies that can selectively induce durable graft versus tumor effects without GVHD. A critical issue in developing specific immunotherapy to augment GVL responses is to determine which minor H antigens are expressed on leukemic stem cells. Studies using transplantation of human AML into SCID mice have identified a putative leukemic stem cell which is contained in the CD34+ CD38- subset of the blast population and is present in very low frequency (<1/200,000) in blood or bone marrow from AML patents. We have examined the ability of minor H antigen-specific CTL to prevent engraftment of human AML in NOD/SCID mice. These studies show that engraftment of leukemias derived from individuals encoding the minor H antigen can be specifically prevented demonstrating that AML stem cells express minor H antigens and are targets for CTL. One approach to determine directly which minor H antigens can be selectively targeted to induce a GVL effect without GVHD is to adoptively transfer T cell clones of defined specificity and function to patients who relapse after HCT. Studies of this approach are now in progress in acute leukemia and have provided important insights into potential obstacles of T cell therapy for relapsed leukemia after HCT.
 ...
PMID:Minor histocompatibility antigens--targets of graft versus leukemia responses. 1243 Sep 18

Differentiation in the hematopoietic system involves, among other changes, altered expression of antigens, including the CD34 and CD38 surface antigens. In normal hematopoiesis, the most immature stem cells have the CD34 + CD34 - phenotype. In acute myeloid leukemia (AML), although blasts from most patients are CD38 +, some are CD38 - . AML blasts are blocked at early stages of differentiation; in some leukemic cells this block can be overcome by a variety of agents, including retinoids, that induce maturation into macrophages and granulocytes both in vitro and in vivo. Retinoids can also induce CD38 expression. In the present study, we investigated the relationship between induction of CD38 expression and induction of myeloid differentiation by retinoic acid (RA) in normal and leukemic human hematopoietic cells. In the promyelocytic (PML) CD34 - cell lines, HL60 and CB-1, as well as in normal CD34 + CD34 - hematopietic progenitor cells RA induced both CD38 expression as well as morphological and functional myeloid differentiation that resulted in loss of self-renewal. In contrast, in the myeloblastic CD34 + leukemic cell lines, ML-1 and KG-1a, as well as in primary cultures of cells derived from CD34 + -AML (M0 and M1) patients, RA caused an increase in CD38 + that was not associated with significant differentiation. Yet, long exposure of ML-1, but not KG-1, cells to RA resulted in loss of self-renewal. The results suggest that while in normal hematopoietic cells and in PML CD34 - cells induction of CD38 antigen expression by RA results in terminal differentiation along the myeloid lineage, in early myeloblastic leukemic CD34 + cells, induction of CD38 and differentiation are not functionally related. Since, several lines of evidence suggest that the CD38 - cells are the targets of leukemic transformation, transition of these cellsinto CD38 + phenotype by RA or other drugs may have therapeutic effect, either alone or in conjunction with cytotoxic drugs, regardless the ability of the cells to undergo differentiation.
 ...
PMID:Retinoic acid induction of CD38 antigen expression on normal and leukemic human myeloid cells: relationship with cell differentiation. 1276 47

Little data exists in Thailand and other Southeast Asian countries regarding the biological characteristics of adult acute myeloid leukemia (AML). In this study, we performed a flow cytometric analysis of 267 Thai adult AML cases to delineate the pattern of leukemic cell surface antigens. Forty-eight cases (18%) were identified as acute promyelocytic leukemia (M3) and 219 cases as non-M3. The most frequent subtype of AML in Thailand was M1/M2 and the least frequent was M7. M3 immunophenotypes were characterized by their unique lack of expression of CD34 and HLA-DR as contrast to the high mean expression of 50% and 70%, respectively, in non-M3. Overall, 60% of cases expressed CD34. Aberrant lymphoid antigens were uniquely seen in specific subtypes of Thai AML, including CD19 (33% of non-M3 vs 23% of M3) and CD2 (12% of M3 vs 2% of non-M3). CD56 was frequently expressed in both M3 and non-M3 while CD16 appeared to be associated with M4/M5 (24% of cases) and CD7 with M1/M2 (21% of cases). Eighty-one percent of non-M3 expressed CD38 while only 53% of M3 did. We found that most Thai adult AML patients were on average 15-20 years younger than those of the West or Japan with only 25% of Thai cases over 60 years of age, although the immunophenotypes were not markedly different. Biological studies of acute leukemia in various countries should help to provide epidemiological clues that play a role in the pathogenesis of leukemia in different geographic regions of the world. Our study represents the largest series of AML ever investigated in the Southeast Asian region.
 ...
PMID:Immunophenotypic profile of adult acute myeloid leukemia (AML): analysis of 267 cases in Thailand. 1503 99

CUB-domain-containing protein 1 (CDCP1) is a novel transmembrane molecule that is expressed in metastatic colon and breast tumors as well as on the surface of hematopoietic stem cells. In this study, we used multiparameter flow cytometry and antibodies against CDCP1 to analyze the expression of CDCP1 on defined hematopoietic cell subsets of different sources. In addition, CDCP1 expression on leukemic blasts and on cells with nonhematopoietic stem/progenitor cell phenotypes was determined. Here we demonstrate that a subset of bone marrow (BM), cord blood (CB), and mobilized peripheral blood (PB) CD34+ cells expressed this marker and that CDCP1 was detected on CD34(+)CD38- BM stem/progenitor cells but not on mature PB cells. Analysis of leukemic blasts from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia in blast crisis revealed that CDCP1 is predominantly expressed on CD34(+)CD133+ myeloid leukemic blasts. However, CDCP1 was not strictly correlated with CD34 and/or CD133 expression, suggesting that CDCP1 is a novel marker for leukemia diagnosis. Stimulation of CD34+ BM cells with CDCP1-reactive monoclonal antibody CUB1 resulted in an increased (approximately twofold) formation of erythroid colony-forming units, indicating that CDCP1 plays an important role in early hematopoiesis. Finally, we show that CDCP1 is also expressed on cells phenotypically identical to mesenchymal stem/progenitor cells (MSCs) and neural progenitor cells (NPCs). In conclusion, CDCP1 is not only a novel marker for immature hematopoietic progenitor cell subsets but also unique in its property to recognize cells with phenotypes reminiscent of MSC and NPC.
 ...
PMID:CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin. 1515 10

Acute myeloid leukaemia (AML) is a life-threatening haematopoietic disease that is characterized by clonal growth and the accumulation of myelopoietic progenitor cells. Although AML cells only have a limited potential to undergo differentiation and maturation, each AML clone is organized in a hierarchical manner similar to normal haematopoiesis. Recent data have shown that each AML clone consists of leukaemic stem cells and their progeny, and that AML stem cells differ from more mature cells in several aspects, including survival and target antigen profiles. Most importantly, AML stem cells, but not their progeny, have the capacity to repopulate haematopoietic tissues with leukaemias in NOD/SCID mice. Furthermore, AML stem cells are thought to be responsible for the infinite growth of leukaemias in patients with AML. The phenotypic properties of AML stem cells have also been described. In most cases, these cells are detectable within the CD34+, CD38-, Lin-, CD123+ subpopulation of AML cells. Because of their AML-initiating and -renewing capacity and their unique phenotype, which includes several molecular targets of drug therapy, AML stem cells have recently been proposed as novel important target cell populations in the context of curative therapies. The present article gives an overview of our knowledge about AML stem cells, their phenotype, and their role as a 'therapy-target' in new concepts to treat and to cure patients with AML.
 ...
PMID:Human leukaemic stem cells: a novel target of therapy. 1529 4

Early plasmacytoid dendritic cell (pDC) leukemia/lymphoma has recently been described as a CD4(+)CD56(+) lineage negative malignancy with characteristic clinical, morphologic, immunophenotypic, and biological features. We present a case of a 72-year-old man who was diagnosed with isolated skin involvement 30 months ago and received numerous chemotherapy cycles that did not prevent three relapses of the disease, the last two involving the bone marrow. The bone marrow was nearly completely infiltrated with small- to medium-sized blasts displaying a high nuclear to cytoplasmic ratio, a cytoplasm with faint basophilia lacking granulations or Auer rods. Small vacuoles surrounding the nucleus were frequently observed. Flow cytometry showed CD4(+), CD56(+), CD45(+), CD38(+), HLA-DR(+), CD33(+), CD123(+), CD2(-), cyCD3(-), CD7(-), CD10(-), CD11b(-), CD13(-), CD14(-), CD16(-), CD19(-), cyCD22(-), CD24(-), CD34(-), CD57(-), CD61(-), CD64(-), CD65(-), cyCD79a(-), CD117(-), MPO(-), and TdT(-) population. At the second bone marrow relapse, CD117 was also positive. Our patient was initially treated with acute myeloid leukemia-type chemotherapy, later he was given acute lymphoblastic leukemia-type treatment, and at the last relapse he received CHOP chemotherapy. Each treatment led to rapid response of tumor manifestations with disease-free intervals of 7 months, 9 months, and 8 months, respectively. Although patients usually have an ominous prognosis, with only 25% living more than 24 months, our patient is alive after 30+ months and has again achieved complete remission after the last chemotherapy.
 ...
PMID:Early plasmacytoid dendritic cell leukemia/lymphoma coexpressing myeloid antigenes. 1531 55

We report 12 cases of t(6;9)(p23;q34)-positive acute myeloid leukemia (AML), all classified using the criteria of the World Health Organization classification. There were 10 women and 2 men with a median age of 51 years (range, 20-76 years). Dysplasia was present in all cases (9 previously untreated), and basophilia was present in 6 (50%). Immunophenotypic studies showed that the blasts were positive for CD9, CD13, CD33, CD38, CD117, and HLA-DR in all cases assessed. CD34 was positive in 11 (92%) of 12, and terminal deoxynucleotidyl transferase was positive in 7 (64%) of 11 cases. The t(6;9) was the only cytogenetic abnormality detected in 7 cases (58%), and 5 cases had additional chromosomal abnormalities. Of 8 cases assessed, 7 (88%) had flt3 gene mutations. We conclude that t(6;9)-positive AML cases have distinctive morphologic features, an immunophenotype suggesting origin from an early hematopoietic progenitor cell, and a high frequency of flt3 gene mutations.
 ...
PMID:Acute myeloid leukemia with t(6;9)(p23;q34) is associated with dysplasia and a high frequency of flt3 gene mutations. 1536 64

The release of soluble forms of CD80 provides a potentially powerful mechanism for the modulation of anti-tumor responses. In this report we investigated whether a soluble form of CD80 (sCD80) circulates in vivo and whether levels are altered in patients with hematological malignancies. Circulating sCD80 was detected by ELISA in all normal donor (0.024-0.318 ng/ml) and patient (0.02-3.75 ng/ml) blood analyzed. The majority of acute myeloid leukemia (13/17) and multiple myeloma (11/12) patients had normal sCD80 levels. Significantly elevated levels were detected in chronic lymphocytic leukemia (CLL, P = 0.0001) and mantle cell lymphoma (MCL, P = 0.0002) patients. MCL patients had the highest levels with 8/9 having levels > 0.318 ng/ml. Increased sCD80 levels in CLL were significantly associated with poor prognosis markers such as low platelet (P = 0.01) and hemoglobin (P = 0.002) levels, elevated WBC counts (P = 0.03) and expression of CD38 (P = 0.048). The immunoreactivity of the sCD80 in both normal and patient plasma was inhibited by the presence of CTLA-4-Ig, suggesting sCD80 is functional. Comparison of sCD80 and soluble CD86 levels demonstrated that these molecules were independently elevated in 39% of patients. The finding that a proportion of CLL and the majority of MCL patients contain elevated levels of sCD80 and the demonstration that sCD80 can interact with CTLA-4-Ig suggests a potential role for sCD80 in modulating anti-tumor responses during the malignant process.
 ...
PMID:Identification of a circulating soluble form of CD80: levels in patients with hematological malignancies. 1537 Feb 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>