scholarly journals A monoclonal antibody identifying a cell surface antigen shared by common acute lymphoblastic leukemias and B lineage cells

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1141-1144 ◽  
Author(s):  
MF Greaves ◽  
W Verbi ◽  
J Kemshead ◽  
R Kennett
Keyword(s):  
Monoclonal Antibody ◽  
B Cells ◽  
Cell Surface ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Fetal Brain ◽  
Lymphocytic Leukemia ◽  
Cell Surface Antigens ◽  
A Cell ◽  
B Lineage

Abstract A monoclonal antibody designated PI153/3, which reacts with neuroblastoma and fetal brain, is shown to identify also a cell surface determinant shared by pre-B and mature B cells and their corresponding leukemias including chronic lymphocytic leukemia, non-Hodgkin's lymphoma, B acute lymphoblastic leukemia, and hairy cell leukemia, but not plasmacytoma. Almost all non-T, non-B acute “lymphoid” leukemias bind PI153/3. The latter includes 71 of 74 common ALL tested, most but not all “unclassified” or “null” ALL and cases of both acute undifferentiated leukemia and Ph1 positive chronic myeloid leukemia in blast crisis with common ALL phenotypes. The antigen is absent or present at very low density on normal and leukemic T lymphocyte, myeloid and erythroid cells. The determinant appears to co-redistribute with cell surface immunoglobulin in B lymphocytes and segregates independently of other cell surface antigens associated with B cells and/or cALL including HLA-DR (Ia-like antigens) and the cALL (gp 100) antigen.

scholarly journals A monoclonal antibody identifying a cell surface antigen shared by common acute lymphoblastic leukemias and B lineage cells

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1141-1144
Author(s):  
MF Greaves ◽  
W Verbi ◽  
J Kemshead ◽  
R Kennett
Keyword(s):  
Monoclonal Antibody ◽  
B Cells ◽  
Cell Surface ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Fetal Brain ◽  
Lymphocytic Leukemia ◽  
Cell Surface Antigens ◽  
A Cell ◽  
B Lineage

A monoclonal antibody designated PI153/3, which reacts with neuroblastoma and fetal brain, is shown to identify also a cell surface determinant shared by pre-B and mature B cells and their corresponding leukemias including chronic lymphocytic leukemia, non-Hodgkin's lymphoma, B acute lymphoblastic leukemia, and hairy cell leukemia, but not plasmacytoma. Almost all non-T, non-B acute “lymphoid” leukemias bind PI153/3. The latter includes 71 of 74 common ALL tested, most but not all “unclassified” or “null” ALL and cases of both acute undifferentiated leukemia and Ph1 positive chronic myeloid leukemia in blast crisis with common ALL phenotypes. The antigen is absent or present at very low density on normal and leukemic T lymphocyte, myeloid and erythroid cells. The determinant appears to co-redistribute with cell surface immunoglobulin in B lymphocytes and segregates independently of other cell surface antigens associated with B cells and/or cALL including HLA-DR (Ia-like antigens) and the cALL (gp 100) antigen.

scholarly journals α4β1 integrin and 190-kDa CD44v constitute a cell surface docking complex for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells

Blood ◽  
2008 ◽  
Vol 112 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Javier Redondo-Muñoz ◽  
Estefanía Ugarte-Berzal ◽  
José A. García-Marco ◽  
Mercedes Hernández del Cerro ◽  
Philippe E. Van den Steen ◽  
...  
Keyword(s):  
Cell Migration ◽  
B Cells ◽  
Cell Surface ◽  
Lymphocytic Leukemia ◽  
Lymphoid Tissues ◽  
Gelatinase B ◽  
A Cell ◽  
Blocking Antibodies ◽  
Hemopexin Domain ◽  
Cell Chronic Lymphocytic Leukemia

Abstract As B-cell chronic lymphocytic leukemia (B-CLL) progresses, malignant cells extravasate and infiltrate lymphoid tissues. Several molecules, including gelatinase B/MMP-9, contribute to these processes. Although mainly a secreted protease, some MMP-9 is present at the B-CLL cell surface and the function, mode of anchoring, and interactions of this MMP-9 are unknown. Here we show that anti–MMP-9 antibodies immunoprecipitated a 190-kDa CD44v isoform and α4β1 integrin from B-CLL cells, but not from normal B cells. Function-blocking antibodies to α4β1 or CD44, or transfection with specific siRNAs, decreased cell-associated proMMP-9 and increased the secreted form. B-CLL cells attached to and bound proMMP-9 and active MMP-9, and this was inhibited by blocking the expression or function of α4β1 or CD44. The MMP-9 hemopexin domain was critical in these interactions. α4β1 and 190-kDa CD44v (but not CD44H) formed a complex at the cell surface, since they both coimmunoprecipitated with anti-α4, anti-β1, or anti-CD44 antibodies. Immunofluorescence analyses confirmed that α4β1 and CD44v colocalized with MMP-9. Binding of proMMP-9 inhibited B-CLL cell migration, and this required MMP-9 proteolytic activity. Thus, we have identified α4β1 and CD44v as a novel proMMP-9 cell surface docking complex and show that cell-associated MMP-9 may regulate B-CLL cell migration and arrest.

Immunoglobulin heavy-chain gene rearrangement in adult acute lymphoblastic leukemia reveals preferential usage of JH-proximal variable gene segments

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2716-2726 ◽  
Author(s):  
Forida Y. Mortuza ◽  
Ilidia M. Moreira ◽  
Maria Papaioannou ◽  
Paula Gameiro ◽  
Luke A. Coyle ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cells ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Acute Leukemias ◽  
Gene Usage ◽  
Vh Gene ◽  
B Lineage

Abstract The aim of this study was to characterize individual-segment and overall patterns of VH gene usage in adult B-lineage acute lymphoblastic leukemia (ALL). Theoretical values of VH segment usage were calculated with the assumption that all VH segments capable of undergoing rearrangement have an equal probability of selection for recombination. Leukemic clones from 127 patients with adult B-lineage acute leukemias were studied by fingerprinting by means of primers for the framework 1 and joining segments. Clones from early preimmune B cells (245 alleles identified) show a predominance of VH6 family rearrangements and, consequently, do not conform to this hypothesis. However, profiles of VH gene family usage in mature B cells, as investigated in peripheral blood (6 samples), B-cell lymphomas (36 clones) and chronic lymphocytic leukemia (56 clones), are in agreement with this theoretical profile. Sequence analyses of 64 VH clones in adult ALL revealed that the rate of VH usage is proportional to the proximity of the VH gene to the JH locus and that the relationship can be mathematically defined. Except for VH6, no other VH gene is excessively used in adult ALL. VH pseudogenes are rarely used (n = 2), which implies the existence of early mechanisms in the pathway to B-cell maturation to reduce wasteful VH-(DH)-JHrecombination. Finally, similar to early immunoglobulin-H rearrangement patterns in the mouse, B cells of ALL derive from a pool of cells more immature than the cells in chronic lymphoid B-cell malignancies.

scholarly journals Asynchronous antigen expression in B lineage acute lymphoblastic leukemia

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 299-307 ◽  
Author(s):  
CA Hurwitz ◽  
MR Loken ◽  
ML Graham ◽  
JE Karp ◽  
MJ Borowitz ◽  
...  
Keyword(s):  
Cell Surface ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Specific Antigen ◽  
Antigen Expression ◽  
Lymphocytic Leukemia ◽  
Hla Dr ◽  
B Lineage ◽  
B Lymphoid ◽  
Developmental Asynchrony

Abstract Cell surface phenotypes of 113 B lineage acute lymphocytic leukemia (ALL) cases, defined by the presence of HLA-DR and at least one B-cell- specific antigen (either CD19, CD20, or CD22), were compared with antigen-defined stages of normal B lymphocyte development. The cases were first evaluated for expression of HLA-DR, CD19, CD34, CD10, CD20, and CD22 by indirect one-color immunofluorescence. Pairwise comparisons of cell surface marker expression were performed for each leukemic sample: no correlations were observed for paired antigen expression on the leukemic samples using antigens expressed either early or late during normal B lymphoid development. Complete immunophenotypes of the cases were then compared with normal B-cell developmental stages. Sixteen different complete immunophenotypes were observed on the leukemias that were not found in normal marrow; at least 78% of the cases demonstrated such “asynchronous” combinations of B lymphoid- associated differentiation antigens. Several samples were subsequently studied by two-color immunofluorescence, and the presence of doubly labeled cells with “asynchronous” antigen combinations was confirmed. These results indicate that the majority of B lineage leukemias exhibit “developmental asynchrony,” as compared with normal marrow B cells. The data further suggest that ALL cases do not accurately represent cells arrested at the stage where the leukemogenic event occurred. Rather, ALL appears to be a disease in which there may be maturation of leukemic blasts; but this maturation is “asynchronous” when compared with the normal developmental process.

scholarly journals Separation of lymphoid and myeloid blasts in the mixed blast crisis of chronic myelogenous leukemia: no evidence for Ig gene rearrangement in CALLA-positive blasts

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1404-1408 ◽  
Author(s):  
K Ha ◽  
MH Freedman ◽  
A Hrincu ◽  
D Petsche ◽  
A Poon ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Cell Lineage ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
B Lineage

Abstract Recent studies suggest that lymphoid blast crisis cells of chronic myelogenous leukemia (CML) expressing the common acute lymphoblastic leukemia antigen (CALLA) are B precursor cells, based on the demonstration of immunoglobulin (Ig) gene rearrangement similar to common acute lymphocytic leukemia. There is little evidence to suggest whether the cells with similar lymphoid characteristics in the mixed blast crisis of CML are also committed to B cell lineage. A patient in “mixed” blast crisis of CML was studied. On the basis of morphology, cytochemistry, and immunological studies, the blasts were classified as having either lymphoid or myeloid characteristics. A proportion of the leukemic blasts expressed CALLA, whereas others expressed My7 antigen. In order to characterize both populations of cell further, CALLA+ blasts and My7+ (myeloid) blasts were isolated by fluorescence- activated cell sorting. The My7+ cells were highly proliferative in cell culture blast colony assays, retained the Ph1 chromosome, and were indistinguishable from acute myelogenous leukemia blasts. The CALLA+ cells were also Ph1-chromosome positive, but in contrast, were poorly proliferative in vitro. Of particular note was their retention of germline configuration of Ig genes, thus distinguishing them from blasts in the lymphoid crisis of CML. We conclude that the lymphoid component in mixed blast crisis may represent a stage of differentiation prior to commitment to B lineage.

scholarly journals P-24: a human leukemia-associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody.

1981 ◽  
Vol 153 (3) ◽  
pp. 726-731 ◽  
Author(s):  
J H Kersey ◽  
T W LeBien ◽  
C S Abramson ◽  
R Newman ◽  
R Sutherland ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Cell Surface ◽  
Surface Structure ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Human Leukemia ◽  
Cell Surface Structure

This study was directed at surface structures that are found on human lymphohemopoietic progenitor cells in normal and leukemic bone marrow. A monoclonal antibody was produced against an acute lymphoblastic leukemia (ALL) cell line of the pre-B phenotype; this antibody (BA-2) was used to demonstrate a cell surface polypeptide of approximately 24,000 mol wt that migrates similarly in both reduced and nonreduced form. This polypeptide, p24/BA-2, was shown by immune precipitation and gel electrophoresis and cell distribution studies to be different from HLA-DR and gp 100/cALLa. p24/BA-2 was present on the surface of 77% (54/70) of cases of non-T, non-B ALL; BA-2 staining was less bright or nondetectable in surface Ig+ (SIg+) chronic lymphocytic leukemia (CLL) and T ALL and nondetectable on peripheral T and B lymphocytes. Approximately 3% of bone marrow mononuclear cells were p24/BA-2+, and these cells were E rosette-, surface (SIg-), and nonphagocytic. Marrow TdT+ progenitor cells were frequently p 24/BA-2+. Results suggest that p24/BA-2 represents a surface structure present on lymphohemopoietic bone marrow progenitor cells and that most common types of ALL bear the p25/BA-2 structure.

CD150 AND CD180 ARE INVOLVED IN REGULATION OF TRANSCRIPTION FACTORS EXPRESSION IN CHRONIC LYMPHOCYTIC LEUKEMIA CELLS

2017 ◽  
Vol 39 (4) ◽  
pp. 291-298 ◽  
Author(s):  
I M Gordienko ◽  
L M Shlapatska ◽  
V M Kholodniuk ◽  
L M Kovalevska ◽  
T S Ivanivskaya ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Surface ◽  
B Cell ◽  
Mrna Expression ◽  
Mrna Level ◽  
Surface Expression ◽  
Lymphocytic Leukemia ◽  
Cell Surface Expression ◽  
B Lineage

Background: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression. From other side we attempted to regulate TFs expression via CD150 and CD180 cell surface receptors. Materials and Methods: Studies were performed on normal peripheral blood B-cell subpopulations and chronic lymphocytic leukemia (CLL) cells isolated from peripheral blood of 67 primary untreated patients with CLL. Evaluation of TFs expression was performed on mRNA level using qRT-PCR and on protein level by western blot analysis. Results: Median of PAX5 and EBF1 mRNA expression was higher in cell surface CD150 positive (csCD150+) compared to csCD150- CLL cases or normal CD19+ and CD19+CD5+ B-cell subsets. Differences in mRNA expression of IRF8, IRF4 and BLIMP1 between studied groups of CLL and normal B cells were not revealed. All CLL cases were characterized by downregulated expression of PU.1 and BCL6 mRNAs in comparison to normal B cells. At the same time elevated SPIB mRNA expression level was restricted to CLL cells. Protein expression of IRF4, IRF8 and BCL6 was uniformly distributed between csCD150- and csCD150+ CLL cases. PU.1 protein and CD20 that is direct PU.1 target gene positively correlated with CD150 cell surface expression on CLL cells. Ligation of CD150 and CD180 alone or in combination upregulated IRF8 and PU.1 while downregulated the IRF4 mRNA expression. Signaling via CD150 or CD180 alone elevated the level of BCL6 mRNA. Strong downregulation of IRF4 mRNA was observed after CD150, CD180 or CD150 and CD180 coligation on CLL cells. We found that in CLL cells CD150 is a negative regulator of SPIB while CD180 is involved in upregulation of EBF1 expression level. Moreover, CD180 ligation on CLL cells caused increase of CD150 mRNA level that is a one of the EBF1 target genes. Conclusions: Analysis of TFs expression profile revealed upregulated SPIB mRNA level and downregulated PU.1 in CLL cells. CD150 and CD180 receptors may modulate transcriptional program in CLL cells by regulating the TFs expression levels.

scholarly journals Separation of lymphoid and myeloid blasts in the mixed blast crisis of chronic myelogenous leukemia: no evidence for Ig gene rearrangement in CALLA-positive blasts

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1404-1408
Author(s):  
K Ha ◽  
MH Freedman ◽  
A Hrincu ◽  
D Petsche ◽  
A Poon ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Cell Lineage ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
B Lineage

Recent studies suggest that lymphoid blast crisis cells of chronic myelogenous leukemia (CML) expressing the common acute lymphoblastic leukemia antigen (CALLA) are B precursor cells, based on the demonstration of immunoglobulin (Ig) gene rearrangement similar to common acute lymphocytic leukemia. There is little evidence to suggest whether the cells with similar lymphoid characteristics in the mixed blast crisis of CML are also committed to B cell lineage. A patient in “mixed” blast crisis of CML was studied. On the basis of morphology, cytochemistry, and immunological studies, the blasts were classified as having either lymphoid or myeloid characteristics. A proportion of the leukemic blasts expressed CALLA, whereas others expressed My7 antigen. In order to characterize both populations of cell further, CALLA+ blasts and My7+ (myeloid) blasts were isolated by fluorescence- activated cell sorting. The My7+ cells were highly proliferative in cell culture blast colony assays, retained the Ph1 chromosome, and were indistinguishable from acute myelogenous leukemia blasts. The CALLA+ cells were also Ph1-chromosome positive, but in contrast, were poorly proliferative in vitro. Of particular note was their retention of germline configuration of Ig genes, thus distinguishing them from blasts in the lymphoid crisis of CML. We conclude that the lymphoid component in mixed blast crisis may represent a stage of differentiation prior to commitment to B lineage.

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