RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 638-649 ◽  
Author(s):  
Mark Holland ◽  
Fernanda V. Castro ◽  
Seema Alexander ◽  
Duncan Smith ◽  
Jizhong Liu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Disease Onset ◽  
Flow Cytometric Analysis ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Cns Disease

Abstract We developed a murine model of CNS disease to obtain a better understanding of the pathogenesis of CNS involvement in pre-B-cell acute lymphoblastic leukemia (ALL). Semiquantitative proteomic discovery–based approaches identified unique expression of asparaginyl endopeptidase (AEP), intercellular adhesion molecule 1 (ICAM1), and ras-related C3 botulinum toxin substrate 2 (RAC2), among others, in an invasive pre-B-cell line that produced CNS leukemia in NOD-SCID mice. Targeting RAC2 significantly inhibited in vitro invasion and delayed disease onset in mice. Induced expression of RAC2 in cell lines with low/absent expression of AEP and ICAM1 did not result in an invasive phenotype or murine CNS disease. Flow cytometric analysis identified an enriched population of blast cells expressing ICAM1/lymphocyte function associated antigen-1 (LFA-1)/CD70 in the CD10+/CD19+ fraction of bone marrow aspirates obtained from relapsed compared with normal controls and those with primary disease. CD10+/CD19+ fractions obtained from relapsed patients also express RAC2 and give rise to CNS disease in mice. Our data suggest that combinations of processes are involved in the pathogenesis of CNS disease in pre-B-cell ALL, support a model in which CNS disease occurs as a result of external invasion, and suggest that targeting the processes of adhesion and invasion unique to pre-B cells may prevent recurrences within the CNS.

scholarly journals Low molecular weight B cell growth factor induces proliferation of human B cell precursor acute lymphoblastic leukemias

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 132-138 ◽  
Author(s):  
B Wormann ◽  
SR Mehta ◽  
AL Maizel ◽  
TW LeBien
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Cell Precursor ◽  
B Cell Growth Factor ◽  
B Cell Precursors

Experiments were conducted to determine the effect of low mol wt B cell growth factor (L-BCGF) on B cell precursor acute lymphoblastic leukemia (ALL). L-BCGF induced a significant increase in 3H-TdR incorporation in 28 of 37 bone marrow aspirates from patients with B cell precursor ALL, with stimulation indices ranging from 2 to 129. Fluorescence-activated cell sorting confirmed that in five of seven patients the common acute lymphoblastic leukemia antigen (CALLA)/CD10 positive leukemic cells were responding directly to L-BCGF. L-BCGF was capable of inducing, in some patients, an increase in absolute viable cells and could also induce colony formation in vitro. The response of B cell precursor ALL was not attributable to beta IL 1, IL 2, or gamma interferon. These results indicate that the majority of B cell precursor ALL undergo a proliferative response to L-BCGF, suggesting a regulatory role for this lymphokine in the growth of B cell precursors.

scholarly journals Clinical and laboratory characteristics of acute leukemia with the 4;11 translocation

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 689-697 ◽  
Author(s):  
J Mirro ◽  
G Kitchingman ◽  
D Williams ◽  
GJ Lauzon ◽  
CC Lin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
Immunoglobulin Gene Rearrangement

Abstract This report describes the clinical and laboratory features of seven cases of acute leukemia associated with the 4;11 chromosomal translocation. All seven children had acute lymphoblastic leukemia by standard morphologic and cytochemical criteria. Leukemic blasts from six of seven patients were terminal deoxynucleotidyl transferase- positive. Immunologic phenotyping suggested the leukemias were of B cell origin; blasts from five patients expressed HLA-DR and p24 (CD-9 antibody), blasts from three patients expressed B4 (CD-19), and blasts from two patients expressed the common acute lymphoblastic leukemia antigen (CD-10). One patient's leukemic blasts contained cytoplasmic immunoglobulin. Analysis of DNA from four of five patients demonstrated additional evidence of B cell differentiation with heavy-chain immunoglobulin gene rearrangement. When DNA from the four patients with heavy-chain immunoglobulin gene rearrangement was analyzed, one patient's DNA demonstrated light-chain immunoglobulin gene rearrangement. However, flow cytometric analysis of blasts from three patients showed the simultaneous expression of the lymphoid-associated antigen B4 (CD-19) and the myeloid-associated antigen My-1 (X-Hapten). Electron microscopic examination of blasts from one patient that expressed both lymphoid- and myeloid-associated antigens demonstrated ultrastructural characteristics of both lineages. These findings suggest that acute leukemia with the t(4;11) abnormality has mixed lineage characteristics as a result of leukemogenesis in a multipotential progenitor cell or aberrant gene expression later in differentiation. Furthermore, serial analysis of karyotype, immunophenotype, and heavy-chain immunoglobulin genes revealed changes in these biologic markers over time, suggesting continued chromosome rearrangement and gene modulation after the leukemogenic event in cells with the t(4;11).

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.

scholarly journals A rare morphological and immunophenotypic presentation of adult B-cell acute lymphoblastic leukemia with blasts in the monocytic zone on CD45 side scatter

2019 ◽  
Vol 5 (3) ◽  
pp. 82
Author(s):  
Shuaeb Bhat ◽  
Saleem Hussain
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Flow Cytometric Analysis ◽  
Blood Film ◽  
High Side

<p class="abstract">We present a case of B-acute lymphoblastic leukemia in an elderly patient who presented with severe weakness and pancytopenia. The patient was a 75 year old Female whose blasts had an unusual morphology in form of coarse azurophilic granules and cytoplasmic blebs and on flow cytometry the blasts were present in the bright CD45 zone with a high side scatter. Bone marrow aspirate sample was subjected to multicolour flow cytometry using Beckman Coulter Navios® which is an 8 colour flow cytometer.  Flow cytometric analysis of the bone marrow aspirate showed blasts in the monocytic zone with a precursor B cell immunophenotype. Complete blood counts showed pancytopenia with peripheral blood film not showing any blasts. Bone marrow aspirate smears showed 20% blasts with coarse azurophilic granules and cytoplasmic blebs. The position of the blasts in this case which were in monocytic zone giving them a bright expression of CD45 and a high side scatter on the CD45 side scatter. This is not the usual position for blasts in B- acute lymphoblastic leukemia as these blasts are less complex. A bright expression of CD45 by blasts in B- acute lymphoblastic leukemia is known to be associated with a poor prognosis but the clinical significance of blasts being bright CD45 with a high side scatter is a very rare occurrence and more number of cases with a similar presentation are required to determine a prognostic significance.</p>

scholarly journals Serum intercellular adhesion molecule-1 in childhood malignancy

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 895-898
Author(s):  
CH Pui ◽  
X Luo ◽  
W Evans ◽  
S Martin ◽  
A Rugg ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adhesion Molecule ◽  
Hodgkin's Disease ◽  
Ewing's Sarcoma ◽  
Wilms Tumor ◽  
Hodgkin’S Disease ◽  
Lymphoblastic Leukemia ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

Levels of soluble intercellular adhesion molecule-1 (ICAM-1) were measured in serum samples taken at diagnosis from pediatric patients with Hodgkin's disease (n = 69), acute lymphoblastic leukemia (n = 28), Wilms' tumor (n = 20), osteosarcoma (n = 17), rhabdomyosarcoma (n = 18), or Ewing's sarcoma (n = 15). Median levels of serum ICAM-1 were significantly higher in acute lymphoblastic leukemia and Hodgkin's disease than in controls and other malignancies. Levels were positively correlated with disease stage for patients with Hodgkin's disease, Ewing's sarcoma or Wilms' tumor, and with the frequency of relapse in Hodgkin's disease (P = .016). Serum levels were normal in all of 76 patients tested in remission. It remains to be determined whether increased serum ICAM-1 levels simply reflect a greater tumor burden or whether this molecule contributes directly to the progression of childhood malignancies.

Adhesion Molecule LFA-1/ICAM-1 Influences on LPS-induced Megakaryocytic Emperipolesis in the Rat Bone Marrow

1997 ◽  
Vol 34 (5) ◽  
pp. 463-466 ◽  
Author(s):  
M. Tanaka ◽  
Y. Aze ◽  
T. Fujita
Keyword(s):  
Bone Marrow ◽  
Single Dose ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Flow Cytometric Analysis ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Flow Cytometric ◽  
Daily Dose

To investigate the effect of adhesion molecules on the occurrence of megakaryocytic emperipolesis of neutrophils, we examined the expression of lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) in the bone marrow of lipopolysaccharide (LPS)-treated rats (experiment I) and the occurrence of megakaryocytic emperipolesis in anti-LFA-1 antibody-treated rats (experiment II). In experiment I, rats were injected with LPS intravenously at a daily dose of 0.5 mg/kg for 3 days. ICAM-1 was intensely stained on megakaryocytes in LPS-treated rats, as detected by flow cytometric analysis. ICAM-1 was immunostained in the megakaryocytes showing emperipolesis. LFA-1 was immunostained in the neutrophils engulfed by megakaryocytes. In experiment II, rats received anti-LFA-1 antibody intravenously at a single dose of 3 mg/kg. One hour after treatment, rats were given LPS intravenously at a single dose of 0.5 mg/kg. The incidence of megakaryocytic emperipolesis was markedly lower in the anti-LFA-1 antibody + LPS group than in the LPS alone group. These findings suggest that the occurrence of megakaryocytic emperipolesis is partly dependent on adhesion molecules via LFA-1/ICAM-1.

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