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)

The carcinoembryonic antigen (CEA) and the classical non-specific cross-reacting antigens (NCAs) belong to the CEA gene family which is part of the immunoglobulin superfamily. In normal hematopoiesis, CEA gene family members (CGMs) have only been reported on cells of myeloid and monocytic origin. In the present study, we analyzed 62 childhood acute lymphoblastic leukemias (ALLs) and seven surface immunoglobulin positive (sig+) B-cell lines for the expression of the CEA family members CEA, NCA-50/90, NCA-95, NCA-160, CGM1 and CGM7. We demonstrated that members of the CEA family were present in 76% of childhood ALLs of B- and T-cell origin. In ALLs of B-cell origin, 82% of the samples expressed at least one CEA subgroup member: 38% NCA-50/90 (CD66c), 31% NCA-160 (CD66a), and 13% both. Six of seven B-cell lines solely expressed NCA-160. In seven ALL of T-cell origin, sole NCA-160 expression was present in 29% of the cases. CEA and CGM1 were not expressed in childhood ALLs or in the sIg+ B-cell lines. In 15 ALLs and seven B-cell lines which could be analyzed for CGM7 expression, the antigen was not detected. NCA-95 was not expressed in 91% of the B-lineage ALLs, in T-lineage ALLs and in the B-cell lines. However, five B-lineage ALLs showed conflicting data on the binding patterns of two, on leukocytes specifically NCA-95 recognizing antibodies suggesting either expression of unknown forms of NCA-95 or NCA-50/90 or of a yet unknown member of the CEA family in these ALL cells. The expression of CEA subgroup members in childhood ALL cells might have prognostic impacts, as an inverse correlation exists between NCA expression on leukemic blasts and the risk factor white blood count at diagnosis.
Leukemia 1994 Dec
PMID:Expression of the CEA gene family members NCA-50/90 and NCA-160 (CD66) in childhood acute lymphoblastic leukemias (ALLs) and in cell lines of B-cell origin. 780

We previously reported a novel monoclonal antibody KOR-SA3544 which predominantly reacted with a surface antigen (sSA3544) expressed on Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL). In the present study, we demonstrate that the antibody specifically recognized nonspecific cross-reacting antigen (NCA)-50/90 (CD66c), one of the carcinoembryonic antigen (CEA)-related glycoproteins encoded by a member of the CEA gene family. In addition, we show that the SA3544 antigen (NCA-50/90) was invariably expressed in cytoplasm of all of the human leukemic cell lines examined (sSA3544-positive B-lymphoid two, sSA3544-negative T or B-lymphoid and non-lymphoid 24) regardless of the presence or absence of surface expression of this antigen. Immunoelectromicroscopic examination revealed that the cytoplasmic antigen was mainly present in granules in sSA3544-positive leukemia cells, whereas it was diffusely present in cytosol in sSA3544-negative leukemia cells. Thus, among members of the CEA family, NCA-50/90 was first demonstrated to be expressed not only on the surface of some leukemia cells, but also in cytoplasm of various types of leukemia cells.
Leukemia 1999 May
PMID:The KOR-SA3544 antigen predominantly expressed on the surface of Philadelphia chromosome-positive acute lymphoblastic leukemia cells is nonspecific cross-reacting antigen-50/90 (CD66c) and invariably expressed in cytoplasm of human leukemia cells. 1037 83

All-trans retinoic acid (ATRA) is used to treat patients with acute promyelocytic leukaemia (APL), inducing APL cells to differentiate into abnormal neutrophils. To investigate the possible relationship between the chromosome translocation t(15;17) found in APL and ATRA treatment, the human myeloid leukaemia cell lines HL60 and NB4, that are PML-RARalpha negative and positive, respectively, were treated with ATRA and immunophenotyped using a CD antibody microarray. For HL60 cells, ATRA induced major increases in descending order of CD38, CD11b, CD45RO, CD11c, CD54 and CD36 with repression of CD117 and CD44. For NB4 cells, ATRA induced major increases in descending order of CD11c, CD54, CD11a, CD11b, CD53, CD65, CD138, CD66c and T-cell receptor alpha/beta (TCRalpha/beta), with repression of CD38 and CD9. The induction of a number of these CD antigens is consistent with the known differentiation of these leukaemias to abnormal neutrophils. Approximately half of the antigens up-regulated by ATRA on NB4 cells were adhesion molecules, including CD11a, CD11b, CD11c, CD54, CD66c and CD138, consistent with the increased adhesiveness of leukaemia cells observed for APL patients treated with ATRA. On HL60 cells, ATRA induced expression of CD38, CD43 and CD45RO and repressed CD117, while the converse was true on NB4 cells that contain chimeric PML-RARalpha. For NB4 cells, ATRA induced some remarkable increases in CD antigens not seen for HL60: CD14 (16.6-fold), CD32 (27.8), CD53 (20.5), CD65 (139), CD66c (79.7), CD126 (15.1), and CD138 (57.6). The expression of these antigens may be regulated by PML-RARalpha in the presence of ATRA. Such CD antigens could be targets for synergistic treatment of APL with therapeutic antibodies following ATRA treatment.
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PMID:All-trans retinoic acid induces different immunophenotypic changes on human HL60 and NB4 myeloid leukaemias. 1756 Dec 54

Here, we show that the platelet-derived growth factor receptor (PDGFR) regulates myeloid and monocytic differentiation of HL-60 myeloblastic leukemia cells in response to retinoic acid (RA) and vitamin D3 (D3), respectively. Both RA and D3 decreased the expression of PDGFR-alpha and PDGFR-beta throughout differentiation. When cells were treated with the PDGFR inhibitor AG1296 in addition to RA or D3, signs of terminal differentiation such as inducible oxidative metabolism and cell substrate adhesion were enhanced. These changes were accompanied by an increased extracellular signal-regulated kinase 1/2 activation. AG1296 also resulted in elevated expression of differentiation markers CD11b and CD66c when administered with RA or D3. Interestingly, other markers did not follow the same pattern. Cells receiving AG1296 in addition to RA or D3 showed decreased G1-G0 arrest and CD14, CD38, and CD89 expression. We thus provide evidence that certain sets of differentiation markers can be enhanced, whereas others can be inhibited by the PDGFR pathway. In addition, we found calcium levels to be decreased by RA and D3 but increased when AG1296 was given in addition to RA or D3, suggesting that calcium levels decrease during myeloid or monocytic differentiation, and elevated calcium levels can disturb the expression of certain differentiation markers.
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PMID:Platelet-derived growth factor receptor regulates myeloid and monocytic differentiation of HL-60 cells. 1769 81

HL-60 human leukemia cells, differentiated into a neutrophil lineage by all-trans retinoic acid (ATRA) treatment, express three members of the carcinoembryonic antigen (CEA) gene family, CEA-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM3 (CD66d), and CEACAM6 (CD66c). CD66d is a neutrophil lineage-specific marker, and CD66a and CD66c are found on epithelial and other cells. HL-60 cells continuously treated with ATRA underwent apoptosis, and cells transiently treated for 1 day underwent cell-cycle arrest, entered into senescence, and exhibited reduced apoptosis with CD66-positive cells accounting for the majority of live cells. CD66 antigens were also induced in NB4 leukemic cells upon continuous treatment with ATRA. NB4 cells underwent apoptosis with a higher frequency in transient versus continuous-treated cells (38% vs. 19% at Day 5), in contrast to HL-60 cells that underwent cell-cycle arrest and senescence when transiently treated with ATRA. CD66 antigens were not induced in transient, ATRA-treated NB4 cells compared with HL-60 cells. Cell-cycle arrest in HL-60 cells involved reduction in expression levels of p21, cyclins D and E, while Rb1 exhibited reduction in protein levels without changes in mRNA levels over the time course of ATRA treatment. Analysis of several proapoptotic proteins implicated the activation of calpain and cleavage of Bax in the intrinsic apoptotic pathway, similar to published studies about the apoptosis of neutrophils. CD1d expression was also induced by ATRA in HL-60 cells and ligation with anti-CD1d antibody-induced apoptosis. In contrast, CD1d-positive primary monocytes were protected from spontaneous apoptosis by CD1d ligation. These studies demonstrate distinct cell fates for ATRA-treated HL-60 cells that provide new insights into ATRA-induced cell differentiation.
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PMID:Differential cell fates induced by all-trans retinoic acid-treated HL-60 human leukemia cells. 1855 5

Highly tumorigenic cancer cell (HTC) populations have been identified for a variety of solid tumors and assigned stem cell properties. Strategies for identifying HTCs in solid tumors have been primarily empirical rather than rational, particularly in epithelial tumors, which are responsible for 80% of cancer deaths. We report evidence for a spatially restricted bladder epithelial (urothelial) differentiation program in primary urothelial cancers (UCs) and in UC xenografts. We identified a highly tumorigenic UC cell compartment that resembles benign urothelial stem cells (basal cells), co-expresses the 67-kDa laminin receptor and the basal cell-specific cytokeratin CK17, and lacks the carcinoembryonic antigen family member CEACAM6 (CD66c). This multipotent compartment resides at the tumor-stroma interface, is easily identified on histologic sections, and possesses most, if not all, of the engraftable tumor-forming ability in the parental xenograft. We analyzed differential expression of genes and pathways in basal-like cells versus more differentiated cells. Among these, we found significant enrichment of pathways comprising "hallmarks" of cancer, and pharmacologically targetable signaling pathways, including Janus kinase-signal transducer and activator of transcription, Notch, focal adhesion, mammalian target of rapamycin, epidermal growth factor receptor (erythroblastic leukemia viral oncogene homolog [ErbB]), and wingless-type MMTV integration site family (Wnt). The basal/HTC gene expression signature was essentially invisible within the context of nontumorigenic cell gene expression and overlapped significantly with genes driving progression and death in primary human UC. The spatially restricted epithelial differentiation program described here represents a conceptual advance in understanding cellular heterogeneity of carcinomas and identifies basal-like HTCs as attractive targets for cancer therapy.
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PMID:Differentiation of a highly tumorigenic basal cell compartment in urothelial carcinoma. 1954 56

Leukemias are the most common malignancy in children, and acute lymphoblastic leukemia (ALL) accounts for 85% of all childhood leukemias. Sequential monitoring of MRD (minimal residual disease) in a set time points during the induction therapy in ALL proves to be a powerful and independent predictor of treatment outcome. Crucial limitation of MRD monitoring by flow cytometry is immunophenotypic changes seen at relapse. Up to now there are single publications about immunophenotypic changes during treatment of ALL in children. Objective was to assess changes in expression of cell antigens during induction treatment of ALL. From May 2005 to January 2008, from among 78 patients with ALL treated in Oncology and Hematology Department, Children's University Hospital in Krakow according to international treatment protocol ALL IC-BFM-2002, 42 were enrolled in assessment of antigens' cells modulation expression during induction. Finally, 24 boys and 18 girls were eligible for evaluation. For MRD detection 4-colour flow cytometry with FACS Diva Software v.5.1 (BD Immunocytometry Systems) was used. The panel of monoclonal antibodies used for MRD detection was based on ALL IC-BFM-2002 standard, modified by additional antibodies combinations from ALL-BFM-2000 protocol. Identification of leukemia associated phenotype (LAP), used for cell analysis in sequential time points, with a set monoclonal antibodies panel, was possible in all analyzed patients. Superficial and cytoplasmic antigens modulation was observed in most of the patients during MRD monitoring. Changes of antigens were seen mostly in PB on day 8 and on day 15 both in PB and BM. The most common antigen modulation found in children with cALL was: downmodulation of CD10, CD34, CD19, and upmodulation of CD45, CD11a, CD20. Unequivocal character of modulation of CD66c, CD58, CD38 was difficult to define (up and downmodulation). Introduction of treatment monitoring based on flow cytometry MRD measurement could lead to further individualization of therapy and improovement of cure rates in ALL, as well as to reducing side effects of ALL treatment and decrease total cost of patient therapy.
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PMID:[Cells antigens' expression modulation during induction treatment of childhood acute lymphoblastic leukemia]. 2134 62

The aim of this study was to identify key markers of minimal residual disease (MRD) in childhood Acute Lymphoblastic Leukemia (ALL). Bone marrow samples were collected at presentation from 139 patients with newly diagnosed B-lineage ALL. On the basis of the expression of CD19, CD10, and CD34 antigens by bone marrow cells, combined with the terminal deoxynucleotide transferase (TdT), CD38, CD45, CD58, CD21, CD66c, CD22, and CD33 expression patterns characterized at diagnosis, leukemia-associated immunophenotypes (LAIPs) were identified. One hundred thirty-nine patients with a median age of 4.3 years were screened with 4-color flow cytometry MRD screening, and 119 of them exhibited 1 or more LAIP suitable for further monitoring, constituting a coverage rate of 85.6%. Only 20 of the 139 (14.4%) had no LAIP identified for follow-up. The most applicable antibody combination was TdT/CD10/CD34/CD19 (87/139, 62.6%), followed by CD38/CD10/CD34/CD19 (85/139, 61.2%) and CD45/CD10/CD34/CD19 (58/139, 41.7%). We have identified a relatively effective MRD panel, combined with TdT, CD38, and CD45 as key markers, that is applicable to the majority of newly diagnosed B-lineage ALL.
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PMID:Key Markers of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia. 2743 18

Minimal residual disease is currently the most powerful prognostic indicator in Precursor B lymphoblastic leukemia. Multiparameter flow cytometry is the most commonly used modality. Seventy three B ALL cases and 15 normal marrows were evaluated for expression patterns of leukemia markers (CD38, CD58, CD73) in all 73 cases and CD66c, CD86 and CD123 in 23 cases. CD73 was aberrantly expressed in 90.41% cases and CD86 in 60.87% B ALL cases. Thus addition of these markers in MRD panels can increase the sensitivity of the assay.
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PMID:Evaluating New Markers for Minimal Residual Disease Analysis by Flow Cytometry in Precursor B Lymphoblastic Leukemia. 2939 99