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

While assessing the prognostic implications of immunophenotyping in 382 patients enrolled in treatment protocols of the Eastern Cooperative Oncology Group (ECOG) for de novo adult acute myeloid leukaemia, we identified 95 patients with a unique antigen profile characterized by high expression of the leucocyte integrin CD11b (CD11b+ AML). High expression of CD11b was defined as > or = 32% positive blasts based on the retrospectively established prognostic cut-off point for this antigen. Although CD11b is normally expressed by mature monocytes, natural killer cells and granulocytes, leukaemic blasts in CD11b+ AML lacked other immunologic monocytic features (e.g. CD14 and CD122, the interleukin-2 receptor beta chain) and demonstrated a high degree of immaturity, as reflected by a high incidence of blasts expressing the stem cell factor receptor, CD117, and few blasts positive for the myeloid differentiation antigen CD15. Furthermore, by FAB criteria, only 41% of CD11b+ AML cases were classified as M4/M5. Patients with CD11b+ AML had a low response rate (54%) when compared with acute monocytic leukaemia (AMOL; 82%, P = 0.006) or AML overall (68%, P = 0.031), independent of age, cytogenetic abnormalities and P-glycoprotein expression. Because of its poor prognosis, recognition of CD11b+ AML is clinically warranted and, given its morphologic and cytogenetic ambiguity, must be based on the unique antigen profile.
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PMID:Acute myeloid leukaemia expressing the leucocyte integrin CD11b-a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis. Eastern Cooperative Oncology Group. 948 12

Immunophenotyping has become common in the diagnosis and classification of acute leukemias and is particularly important in the proper identification of cases of minimally differentiated acute myeloid leukemia (AML-M0). To evaluate the immunophenotype of adult AML, 106 cases were studied by cytochemical analysis and by flow cytometry with a panel of 22 antibodies. The results were compared with the French-American-British (FAB) Cooperative Group classification, as well as with available cytogenetic data on each case. CD45, CD33, and CD13 were the most commonly expressed antigens (97.2%, 95.3%, and 94.3%, respectively). Lymphoid-associated antigens were expressed in 48.1% of cases. CD20 was the most commonly expressed lymphoid antigen (17%), although often expressed in only a subpopulation of leukemic cells, followed by CD7 (16%), CD19 (9.8%), CD2 (7.5%), CD3 (6.7%), CD5 (4.8%), and CD10 (2.9%). Some immunophenotypes correlated with FAB type, including increased frequency of CD2 expression in AML-M3; lack of CD4, CD11c, CD36, CD117, and HLA-DR expression in AML-M3; increased frequency of CD20 and CD36 expression and lack of CD34 expression in AML-M5; increased frequency of CD5 expression in AML-M5a; and increased frequency of CD14 expression in AML-M5b, when compared with all other AMLs (P < .05). When compared with AML-M5b, AML-M5a demonstrated a lack of CD4 expression and a high frequency of CD117 expression. Complete morphologic and cytogenetic agreement between AML-M3 and t(15;17) was present, and four of five cases of AML-M4Eo demonstrated inv(16). The remaining case of M4Eo was characterized by a 6;9 translocation, and two other inv(16) cases were not classified as M4Eo. Expression of CD2 was present in two t(15;17) cases and in one inv(16) case, but expression of this antigen was not restricted to AML cases with these karyotypic abnormalities. Similarly, expression of CD19 was not specific for t(8;21) AML. All t(8;21) leukemias demonstrated M2 morphology. With the exception of M3, M4Eo, and a subgroup of M2 leukemias, the FAB classification does not appear to define cytogenetically distinct disease groups in adult AML. Immunophenotypically distinct profiles were identified in the M3 and M5 morphologic groups of the FAB classification. Immunophenotyping studies are helpful in the determination of myeloid lineage. In general, however, they are not sufficiently specific alone to be useful in precisely identifying either FAB or cytogenetically defined disease subtypes.
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PMID:The immunophenotype of adult acute myeloid leukemia: high frequency of lymphoid antigen expression and comparison of immunophenotype, French-American-British classification, and karyotypic abnormalities. 958 94

We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819 acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4 undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of the French-American-British (FAB) subtype, one third of BAL, all four AUL, but only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified as: T-cell lineage (two thirds), mainly pro-T-ALL or T-I, and B lineage (one third); cells from 62% of these ALL cases coexpressed other myeloid markers (CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML or ALL cases according to age being similar in the adult and pediatric groups. Our findings demonstrate that c-kit is a reliable and specific marker to detect leukemia cells committed to the myeloid lineage, and therefore should be included in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid commitment of the blasts. c-kit expression should score higher, at least one point, in the system currently applied to the diagnosis of BAL, as its myeloid specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c-kit identifies a subgroup of cases, which may correspond to leukemias either arising from early prothymocytes and/or early hematopoietic cells, both able to differentiate to the lymphoid and myeloid pathways.
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PMID:The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). 965 60

The c-kit proto-oncogen (CD 117) has been shown to be present in several cell types including normal and neoplastic hemopoietic cells. Among normal BM cells, CD117 expression has been found in about half of the CD34+ precursors including progenitors committed to the erythroid, granulo-monocytic, and megakaryocytic cell lineages. In addition, strong CD117 expression is detected in bone marrow mast cells as well as in a small subset of NK cells displaying strong reactivity for CD56, and in a relatively important proportion of CD3 /CD4 /CD8 prothymocytes. These results suggest that CD117 expression can be detected in both myeloid and lymphoid lineages although for the lymphoid lineage it would be restricted to a small NK-cell subset and early T-cell precursors. In acute leukemias CD117 expression was initially associated with AML. Nevertheless, at present it is well established that CD 117 expression may also be found in a relatively important proportion of T-ALL while it is usually absent in B-lineage ALL. Moreover, recent studies have shown that in about one-third of multiple myeloma cases and patients with monoclonal gammopathy of undetermined significance plasma cells display reactivity for CD1117. The prognostic influence of CD117 expression has not yet been clearly established. The analysis of this marker may also be of value for the investigation of minimal residual disease (MRD). It has been suggested that CD117 in combination with other antigens may be of great help for the identification of leukemia-associated phenotypes that could be used to monitor MRD in both acute myeloid leukemias and multiple myeloma patients achieving morphological complete remission.
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PMID:Expression of the c-kit (CD117) molecule in normal and malignant hematopoiesis. 971 8

The primary role of protooncogene c-kit in mast cell differentiation is supported by the development of mast cells from CD34+/CD117+(c-kit) myeloid precursors. Growth factor independence, neoplastic transformation and differentiation of mast cells were found in association with c-kit activating mutations in both murine and human mastocytoma and mast cell diseases. We have identified a novel c-kit mutation (D816Y) in peripheral blood mononuclear cells from a patient with AML (M2), massive presence of mast cells in bone marrow and rapid progression of the disease. The mutation, a G-->T transversion at nt 2467 of the c-kit gene resulting in Asp816-->Tyr substitution, corresponds to the D814Y and D817Y mutations identified and characterized in the murine P815 mastocytoma and the rat RBL-2H3 mast cell leukemia cell lines. The absence of SCF transcripts that we found by RTPCR in the patient's blasts indicates that, also in humans, this activating mutation leads to SCF independent growth. The expression of the mutant allele on Kit signaling may be further enhanced by trisomy of chromosome 4 (carrying the c-kit gene) in the patient's blasts. From these findings it is concluded that mast cells could be generated from a leukemic CD34/CD117-positive clone, that combines the antigenic expression of mast cell precursor to the growth and differentiation factor-independence which was derived by the c-kit D816Y mutation.
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PMID:In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation. 971 3

C-KIT, TIE and HKT expression on leukemic cells from patients were simultaneously analyzed using flow cytometry. Consistent with previous reports, leukemic cells from most patients with de novo acute myeloid leukemia (AML) were C-KIT-positive (28/35), while those from patients with B-lineage acute lymphoid leukemia (B-ALL) were C-KIT-negative (0/9). In the B-ALL patients, leukemic cells trom seven patients had one or more myeloid antigen such as CD13, CD15 and CD33. In contrast to C-KIT expression, leukemic cells from only one patient with acute monocytic leukemia were TIE-positive. Similarly, leukemic cells from only two patients (one, B-ALL with t(4;11)(q21;q23) and one, essential thrombocythemia in myeloblastic transformation (ET-MBT)) were HTK-positive. These results suggest that among the three receptor tyrosine kinases, C-KIT is the most useful marker for identifying AML.
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PMID:Analysis of C-KIT, TIE and HTK expression on leukemic cells using flow cytometry: a preliminary report. 971 14

Acute myeloid leukaemia (AML) cells express the SCF receptor c-kit (CD117) on their cell surface and demonstrate enhanced adhesion to fibronectin (FN) following exposure to stem cell factor (SCF). Increased adhesion occurs within 5 min, is dose dependent, and persists beyond 2 h. Baseline and enhanced adhesion occur through the surface FN receptor very late antigen-5 (VLA-5, CD49e/CD29) which is expressed by AML cells. Unstimulated AML cells exposed to FN undergo less apoptosis than controls (inhibition 22.5 +/- 7.0%, P = 0.02, n = 8). Exposure to SCF alone without FN also inhibits AML cell apoptosis (by 19.0 +/- 7.7% compared to controls, P = 0.06, n = 8). Simultaneous exposure to SCF and FN increases the inhibition of AML cell apoptosis to 37.8 +/- 7.9% (P = 0.005 compared to control, P = 0.04 compared to FN alone, P = 0.06 compared to SCF alone) demonstrating that SCF not only enhances the propensity of AML cells to adhere to FN, but also results in an additive survival benefit following FN contact. Some but not all the reduction in apoptosis is mediated through VLA-5. The combination of SCF and FN also affects proliferation, resulting in a synergistic enhancement of AML cell proliferation in half the cases studied. When normal CD34+ human haemopoietic progenitors were studied, FN had little effect on their apoptosis and failed to enhance the anti-apoptotic effect of SCF. It did, however, synergise with SCF in promoting CD34+ cell proliferation. Exposure of AML cells to SCF and FN, both of which can be found in high concentration in the bone marrow stroma, inhibits apoptosis. Cytokines and extracellular matrix proteins augment each others' effects since SCF enhances adhesion to fibronectin, which in turn augments the survival signal delivered by the cytokine alone. Cytokine and adhesion receptors can combine to affect cell characteristics including proliferation and survival.
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PMID:Stem cell factor enhances the adhesion of AML cells to fibronectin and augments fibronectin-mediated anti-apoptotic and proliferative signals. 973 85

Expression of I and sialosyl-I antigens was examined using specific monoclonal antibodies. The anti-I antibody C6 reacted with monocytes (24%), T cells (55%), B cells (80%) but not with neutrophils (4%), bone marrow (BM) CD34+ cells (2%) or mobilized peripheral blood (PB) CD34+ cells (1%). The anti-sialosyl-I antibody NUH2 reacted with monocytes (38%) and BM CD34+ cells (41%) but not with T cells (2%), B cells (0%) or neutrophils (1%) and it hardly reacted with mobilized PB CD34+ cells (8%). Flow cytometric analyses of CD34+ cells enriched from BM showed that most of the sialosyl-I cells expressed CD13, CD33, CD117, and HLA-DR. Sialosyl-I+ CD34+ cells isolated from BM produced a large number of granulocyte-macrophage colonies and macrophage colonies. Therefore, sialosyl-I+ CD34+ cells are suggested to be colony-forming units granulocyte-macrophage (CFU-GM) and colony-forming units macrophage (CFU-M). BM CD34+ cells cultured in medium containing cytokines produced I+ CD14+ monoblasts and sialosyl-I+ CD14+ monoblasts. Leukemic cells from patients with acute myeloid leukemia were I-negative (32/32) and sialosyl-I-positive (one/32). Leukemic cells from patients with acute lymphoid leukemia were I-positive (four/ten) and sialosyl-I-negative (ten/ten). These results indicate that (1) the I antigen is broadly expressed by monoblasts, monocytes, lymphocytes, and leukemic lymphoblasts, and (2) the sialosyl-I antigen is expressed along the normal differentiation of CFU-GM to monocytes.
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PMID:Expression profiles of I and sialosyl-I antigens on blood cells: the sialosyl-I antigen is expressed along the monocytic differentiation. 978 6

To extend the panel of monoclonal antibodies useful for immunophenotyping of acute leukemias, two new reagents, TC-12 and TH-111, were developed. TC-12 was found "unique," and TH-111 was assigned to the recently defined CD96 cluster. Both reagents show little reactivity with blood and bone marrow nucleated cells but define a major (TH-111: 78.3%) or an important (TC-12: 45.6%) subset of T-cell acute lymphoblastic leukemia (ALL). In addition, in acute myeloid leukemia (AML), the expression of TC-12 was found in 64 (20.2%) of 317 and TH-111 in 97 (29.1%) of 333 of these patients. TC-12 positivity in AML was virtually restricted to the Fab subtypes M0, M1, M2, and M6. In the group of immature AML characterized by the coexpression of CD7 as well as CD117 and CD34 positivity, leukemic blasts frequently disclosed the TC-12 and TH-111 antigen. Although the TC-12 antigen could not be determined, TH-111 immunoprecipitated the TACTILE (CD96) antigen and, when expressed, was found to be associated with the transferrin receptor. These reagents may help not only to define and dissect T-cell ALL, but also to characterize a subgroup of immature AML at the divergence of T-cell and myeloid lineage.
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PMID:Antibodies TC-12 ("unique") and TH-111 (CD96) characterize T-cell acute lymphoblastic leukemia and a subgroup of acute myeloid leukemia. 984 76

A subset of patients with systemic mastocytosis (SM) develop acute myeloid leukaemia (AML). However, little is known about the biology of such leukaemias and their relationship to the mast cell (MC) lineage. We report on two female patients who suffered from SM and AML. According to FAB criteria, the leukaemias were classified as AML-M4 (patient 1) and AML-MO (patient 2). The coexistence of the two distinct neoplasms (AML and SM) was demonstrable by immunostaining of serial bone marrow (BM) sections with monoclonal antibodies (mAb). In particular, the MC infiltrates were found to react with mAb against MC-tryptase and MC growth factor receptor c-kit (CD117), but not with mAb to CD15 or CD34. In contrast, the AML blasts were immunoreactive for CD15 (patient 1) or CD34 (patient 2), but did not express tryptase. The c-kit point mutation Asp-->Val at codon 816, considered to play a role in the transformation of MC progenitors, was detected in patient 1 in a BM cell fraction containing 4% MC. However, no c-kit mutation was found in pure AML blasts (<1% MC). These findings argue against an evolution of the AML clone from neoplastic MC or MC-committed progenitors.
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PMID:Systemic mastocytosis associated with acute myeloid leukaemia: report of two cases and detection of the c-kit mutation Asp-816 to Val. 985 25


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