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 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

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 Immunologic classification of lymphocytic leukemias based on monoclonal antibody-defined cell surface antigens

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 207-215
Author(s):  
RW Schroff ◽  
KA Foon ◽  
RJ Billing ◽  
JL Fahey
Keyword(s):  
Cell Surface ◽  
B Cell ◽  
Cell Lineage ◽  
Antigen Expression ◽  
Surface Antigens ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Cell Surface Antigens ◽  
Prolymphocytic Leukemia ◽  
Hla Dr

A panel of monoclonal antibodies reactive with normal lymphocyte subsets was used to classify cases of lymphocytic leukemia on the basis of cell surface antigen expression. The antibodies employed were commercially available and included a common framework HLA-DR antibody, two pan-T antibodies (Leu-1 and OKT-3), and antibodies defining cytotoxic/suppressor (Leu-2 and OKT-8) and helper/inducer (Leu-3 and OKT-4) subpopulations of normal T lymphocytes. Cases of ALL could be subgrouped into non-T non-B, pre-T and T-ALL on the basis of reactivity with HLA-DR, Leu-1, and OKT-3 antibodies. Leukemic cells from patients with T-cell CLL could be divided into Leu-2/OKT-8 reactive and Leu- 3/OKT-4 reactive subpopulations, as well as a subgroup in which the majority of cells were unreactive with either of these antibodies. With the exception of one individual, all Sezary cell leukemias expressed a phenotypic pattern similar to that of the Leu-3 subgroup of T-CLL. Malignancies of B-cell lineage (B-CLL, prolymphocytic leukemia, and lymphosarcoma) that were examined were reactive with both the HLA-DR and Leu-1 antibodies. On the contrary, normal B lymphocytes and lymphoid cell lines of B-cell origin did not express surface antigens recognized by the Leu-1 antibody.

scholarly journals Immunologic classification of lymphocytic leukemias based on monoclonal antibody-defined cell surface antigens

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 207-215 ◽  
Author(s):  
RW Schroff ◽  
KA Foon ◽  
RJ Billing ◽  
JL Fahey
Keyword(s):  
Cell Surface ◽  
B Cell ◽  
Cell Lineage ◽  
Antigen Expression ◽  
Surface Antigens ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Cell Surface Antigens ◽  
Prolymphocytic Leukemia ◽  
Hla Dr

Abstract A panel of monoclonal antibodies reactive with normal lymphocyte subsets was used to classify cases of lymphocytic leukemia on the basis of cell surface antigen expression. The antibodies employed were commercially available and included a common framework HLA-DR antibody, two pan-T antibodies (Leu-1 and OKT-3), and antibodies defining cytotoxic/suppressor (Leu-2 and OKT-8) and helper/inducer (Leu-3 and OKT-4) subpopulations of normal T lymphocytes. Cases of ALL could be subgrouped into non-T non-B, pre-T and T-ALL on the basis of reactivity with HLA-DR, Leu-1, and OKT-3 antibodies. Leukemic cells from patients with T-cell CLL could be divided into Leu-2/OKT-8 reactive and Leu- 3/OKT-4 reactive subpopulations, as well as a subgroup in which the majority of cells were unreactive with either of these antibodies. With the exception of one individual, all Sezary cell leukemias expressed a phenotypic pattern similar to that of the Leu-3 subgroup of T-CLL. Malignancies of B-cell lineage (B-CLL, prolymphocytic leukemia, and lymphosarcoma) that were examined were reactive with both the HLA-DR and Leu-1 antibodies. On the contrary, normal B lymphocytes and lymphoid cell lines of B-cell origin did not express surface antigens recognized by the Leu-1 antibody.

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 Induction of HLA-DC/DS (LEU 10) antigen expression by human precursor B cell lines.

1983 ◽  
Vol 158 (5) ◽  
pp. 1757-1762 ◽  
Author(s):  
C Y Wang ◽  
A Al-Katib ◽  
C L Lane ◽  
B Koziner ◽  
S M Fu
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Antigen Expression ◽  
Fold Increase ◽  
Cell Interaction ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Hla Dr

The expression of HLA-DC/DS antigen detected by the monoclonal antibody Leu 10 was studied in three human precursor and pre-B cell lines (Josh 7, Reh, and Nalm 12). Flow cytometric analysis showed that none of these cell lines stained for the HLA-DC/DS antigen. In the presence of 1.6 X 10(-9) M of 12-O-tetradecanoylporbol-13-acetate (TPA), expression of this antigen was detected. The expression was completed after 168 h of incubation. Iodination of cell surface, immunoprecipitation by Leu 10 antibody, and two-dimensional gel analysis revealed that TPA-treated Josh 7 cells synthesized and expressed a 29,34 kD bimolecular complex with both alpha and beta chains different from those of HLA-DR antigen. Quantitative absorption experiments with cell lysates indicated a greater than 25-fold increase in HLA-DC/DS antigen in TPA-treated cells. With the induction of HLA-DC/DS antigen expression, there are concomitant decreases in the expression of the common acute lymphoblastic leukemia antigen (CALLA) and the enzymatic activity of terminal deoxynucleotidyl transferase. No appreciable changes in HLA-DR and Ig expression were observed. There was also no change in HLA-SB expression as detected by antibody ILR-1. However, DNA synthesis was markedly inhibited by TPA treatment. These results indicate that precursor and pre-B cell lines can be induced to mature in vitro. They also suggest that the expression of HLA-DC/DS antigen which precedes the expression of membrane Ig and follows the HLA-DR expression is relevant to human B cell development and cell interaction.

Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 836-840 ◽  
Author(s):  
DY Mason ◽  
H Stein ◽  
J Gerdes ◽  
KA Pulford ◽  
E Ralfkiaer ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Types ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Lymphoid Cells ◽  
Tissue Sections ◽  
B Lymphoid ◽  
Anti Cd20

Two monoclonal antibodies (To15 and 4KB128) specific for the B cell- associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti- CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti- CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface.

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 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.

Haploinsufficiency of Ebf1 Collaborates with BCR-ABL1 to Decrease the Latency of Acute Lymphoblastic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3363-3363
Author(s):  
Salil Goorha ◽  
Noel T. Lenny ◽  
Christopher B Miller ◽  
S. Scott Perry ◽  
Xiaoping Su ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cells ◽  
B Cell ◽  
Copy Number ◽  
Lymphoblastic Leukemia ◽  
B Cell Development ◽  
B Lineage ◽  
B Lymphoid

Abstract In previously published genome-wide copy number analysis of leukemic samples from 242 pediatric acute lymphoblastic leukemia (ALL) patients, we reported that mutations in genes regulating B lymphoid development are the most common lesion in B-progenitor ALL, and these include PAX5, IKZF1, and EBF1. Mono-allelic deletion of EBF1 was observed in 8/200 B-progenitor leukemia samples, including a BCR-ABL1 ALL. EBF1 encodes a transcription factor that is required for the development of B cells, and with E2A regulates the expression of B-lineage specific genes. Mice null for Ebf1 arrest B cell development at the pro-B cell stage, whereas Ebf1+/− mice have a 50% reduction in the number of immature and mature B cells but a normal number of pro-B cells. Importantly, neither haploinsufficiency nor the complete loss of Ebf1 results in the development of leukemia in mice. To examine the role of genetic alterations targeting B-lymphoid differentiation in the pathogenesis in BCR-ABL1 ALL, we transduced Ebf1+/+ and Ebf1+/− bone marrow cells with MSCV-GFP-IRES-p185 BCR-ABL1 retrovirus and transplanted the resultant cells into lethally irradiated wild-type C57BL6 recipient mice. Mice transplanted with BCR-ABL1 Ebf1+/− cells developed B lineage ALLs at a shorter latency than observed with BCR-ABL1 Ebf1+/+ cells (median overall survival of 17 days in Ebf1+/− vs 42 days in Ebf1+/+, P<0.0001). All leukemias had a B220+Cd19+Bp1+ pre-B cell immunophenotype; however, the leukemias that developed from the Ebf1+/− cells aberrantly expressed high levels of the stem cell marker Sca1 (mean fluorescence level for Sca1 of 69.6 in Ebf1+/− (n=22) vs 16.8 in Ebf1+/+ (n=14), p<0.0001). To begin to understand how a decrease in the copy number of Ebf1 may contribute to leukemogenesis, we examined early B cell development in bone marrow (BM) cells from two week-old C57BL6 Ebf1+/− and Ebf1+/+ mice. Our analysis confirmed previous reports indicating a 2-fold reduction of B220+CD43− B cells in Ebf1+/− compared to Ebf1+/+ mice. Interestingly, however, we also detected an approximately 6-fold increase in a transitional population of B220loIL-7R+cKitlo Pre-pro B cells that also expressed Sca1 (2194 mean number of Ebf1+/− cells per 100,000 BM cells (n=10) vs 372 mean number of Ebf1+/+ cells per 100,000 BM cells (n=8), p<0.0001), an observation that raises the possibility that Ebf1 haploinsufficiency expands the pool of cells that are susceptible to transformation by BCR-ABL expression. It will be important to examine whether the accelerated tumorigenesis resulting from Ebf1 haploinsufficiency is a consequence of a subtle shift in differentiation, or some alternative mechanism of oncogenic cooperativity. Studies are underway to directly assess the role of B220loIL-7R+cKitlo Sca1+ cells in BCR-ABL1 driven ALL.

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