scholarly journals The occurrence of the HL-B alloantigens on the cells of unclassified acute lymphoblastic leukemias.

1975 ◽  
Vol 142 (5) ◽  
pp. 1334-1338 ◽  
Author(s):  
S M Fu ◽  
R J Winchester ◽  
H G Kunkel
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Lymphoblastic Leukemia ◽  
Sheep Erythrocyte ◽  
Cell Lineage ◽  
The Other ◽  
Surface Markers ◽  
Positive Group ◽  
Lymphocyte Surface Markers

Six cases of acute lymphoblastic leukemia were studied by a variety of T- and B-lymphocyte surface markers. Two appeared to represent T-cell leukemias with the lymphoblasts forming sheep erythrocyte rosettes. The other four lacked all the usual membrane markers. However, indirect immunofluorescence with alloantisera detected the presence of the Ia-related HL-B antigens on the cells of the latter four cases; these antigens were absent in the first two cases. The primary association of the HL-B antigens with B cells raises the possibility that the positive group of cases are of B-cell lineage.

Mature B-Cell Acute Lymphoblastic Leukemia With Associated Translocations (14;18)(q32;q21) and (8;9)(q24;p13)

2003 ◽  
Vol 127 (5) ◽  
pp. 610-613
Author(s):  
Cherie H. Dunphy ◽  
Hendrik W. van Deventer ◽  
Kathryn J. Carder ◽  
Kathleen W. Rao ◽  
Georgette A. Dent
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
The Other ◽  
Review Of The Literature ◽  
Marker Chromosomes ◽  
Cell Acute Lymphoblastic Leukemia

Abstract The translocation t(14;18)(q32;q21) is most commonly associated with follicular lymphoma but has also been described in acute lymphoblastic leukemia (ALL) of B-cell origin. Although these ALL cases have had a pre-pre-B, pre-B, or mature B-cell immunophenotype and L2 or L3 morphology, all have been associated with an abnormality of 8q24. In fact, 91% (10 of 11) have been associated with t(8;22) or t(8;14), marker chromosomes for Burkitt-type ALL. The other case was associated with del(8)(q24). Thus, Burkitt-type ALL may have various immunophenotypes and morphology when associated with t(14;18). We describe a case of mature B-cell ALL associated with t(14;18) and t(8;9)(q24;p13). The morphology was suggestive but not entirely characteristic of the L3 subtype. However, on the basis of the cytogenetic findings and the review of the literature, perhaps this case represents a variant of Burkitt-type ALL, which would be important to recognize for prognostic and therapeutic purposes. We describe our findings and review the literature to heighten awareness of this group of ALLs associated with t(14;18). Additional cases need to be accrued and documented to determine the significance of an associated abnormality of 8q24 in this setting.

Effects of Rituximab on JAK-STAT and NF-κB signaling pathways in acute lymphoblastic leukemia and chronic lymphocytic leukemia

2019 ◽  
Vol 44 (4) ◽  
pp. 499-509 ◽  
Author(s):  
Ayşegül Dalmızrak ◽  
Nur Selvi Günel ◽  
Burçin Tezcanlı Kaymaz ◽  
Fahri Şahin ◽  
Güray Saydam ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Signaling Pathways ◽  
Cell Lines ◽  
B Lymphocyte ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Protein Expressions ◽  
Apoptotic Effect

AbstractObjectivesRituximab is a monoclonal antibody that targets the B-lymphocyte surface antigen CD20. It is used in the treatment of some diseases including B-cell chronic lymphocytic leukemia (B-CLL). There are a lot of data regarding effect of Rituximab on lymphoma cells. But, there is no satisfactory information about the effect of Rituximab on the signaling pathways in leukemia cells. In this study, it was aimed to understand the effect of Rituximab on JAK-STAT and NF-κB signaling pathways in B-cell acute lymphoblastic leukemia (B-ALL) and B-CLL.Material and methodsApoptotic effect of Rituximab in the TANOUE (B-ALL) and EHEB (B-CLL) cell lines were evaluated by using the Annexin V method. mRNA expression levels of STAT3 and RelA were analysed by quantitative RT-PCR (Q-PCR). Alterations in STAT3 and RelA protein expressions were detected by using a chromogenic alkaline phosphatase assay after Western Blotting.ResultsRituximab had no apoptotic effect on both cell lines. Complement-mediated cytotoxicity was only detected in EHEB cells. mRNA and protein expressions of STAT3 and RelA genes were decreased following Rituximab treatment.ConclusionOur preliminary results suggest that the use of Rituximab might be effective in B-ALL though both signaling pathways.

scholarly journals Acute leukemia with Burkitt's tumor cells: A study of six cases with special reference to lymphocyte surface markers

Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 183-188 ◽  
Author(s):  
G Flandrin ◽  
JC Brouet ◽  
MT Daniel ◽  
JL Preud'homme
Keyword(s):  
Electron Microscopy ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Tumor Cells ◽  
Lymphoblastic Leukemia ◽  
Surface Markers ◽  
Lymphocyte Surface Markers ◽  
Surface Immunoglobulins ◽  
Blast Cells

Abstract In six patients with acute leukemia (about 2% of the patients referred for acute lymphoblastic leukemia) the blast cells invading bone marrow and blood showed all the cytologic, cytochemical, and electron microscopy features of Burkitt's tumor cells. The presence of monoclonal surface immunoglobulins (their synthesis being proved by in vitro culture experiments), the binding of IgG aggregates, and the absence of rosette formation with sheep red cells documented the monoclonal B-cell origin of these blast cells which is in sharp contrast to the findings in common acute lymphoblastic leukemia. The course of the disease was usually rapidly fatal without chemotherapy- induced remission.

Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia [see comments]

Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1247-1258
Author(s):  
E Thiel ◽  
BR Kranz ◽  
A Raghavachar ◽  
CR Bartram ◽  
H Loffler ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Sheep Erythrocyte ◽  
Treatment Protocol ◽  
Cell Lineage ◽  
T Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Hematopoietic Progenitor Cell ◽  
Hla Dr

Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia (ALL) were immunophenotyped as part of a prospective treatment protocol study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation, but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins mostly in perinuclear accumulation. The T- cell surface antigens CD5 and/or CD2 and focal acid phosphatase were additional markers of this subgroup traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell markers, namely terminal deoxynucleotidyl transferase (TdT), and in part common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique antigen of marrow cells absent in thymus cells, further characterized this immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was supported by germ-line T-cell receptor beta genes found in 21 of 36 patients analyzed. In five cases only T gamma-chain genes were rearranged. Fifteen patients, however, had rearrangements of both T beta and T gamma genes. Immunoglobulin heavy chain genes were rearranged only in two cases. Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting clinical features, namely mediastinal mass, lymphoadenopathy, and platelet count, and independently of clinical factors in prognosis (P = .02, median remission duration: 15.7 v 33.5 months, and P = .02, median survival time: 24.6 v 50.7 months). We conclude that ALL classification based solely on T- or B-cell lineage affiliation is not sufficient but needs further subdivision according to relevant maturation stages as exemplified here within the T-cell axis. The putative prethymic T cell progenitor phenotype described might help elucidate the sequence of genetic events that commit normal hematopoietic cells to the T-cell lineage.

Lymphocyte Surface Markers in Acute Lymphoblastic Leukemia of Adults

1977 ◽  
Vol 68 (5) ◽  
pp. 543-546 ◽  
Author(s):  
Juan C. Garcia ◽  
Yi-Hsiang Chen ◽  
Clement C. S. Hsu
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Surface Markers ◽  
Lymphocyte Surface ◽  
Lymphocyte Surface Markers

scholarly journals Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia

Blood ◽  
2011 ◽  
Vol 118 (10) ◽  
pp. 2801-2808 ◽  
Author(s):  
Kristen M. Sokalski ◽  
Stephen K. H. Li ◽  
Ian Welch ◽  
Heather-Anne T. Cadieux-Pitre ◽  
Marek R. Gruca ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Acute Lymphoblastic Leukemia ◽  
B Cells ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
B Cell Differentiation ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Ets Transcription Factor

Abstract The E26 transformation-specific (Ets) transcription factor PU.1 is required to generate lymphoid progenitor cells from hematopoietic stem cells, but it is not required to generate B cells from committed B-cell lineage progenitors. We hypothesized that PU.1 function in B-cell differentiation is complemented by the related Ets transcription factor Spi-B. To test this hypothesis, mice were generated lacking both PU.1 and Spi-B in the B-cell lineage. Unlike mice lacking PU.1 or Spi-B, mice deficient in both PU.1 and Spi-B in the B-cell lineage had reduced frequencies of B cells as well as impaired B-cell differentiation. Strikingly, all PU.1 and Spi-B–deficient mice developed pre-B cell acute lymphoblastic leukemia before 30 weeks of age. Pre-B cells accumulated in the thymus resulting in massive thymic enlargement and dyspnea. These findings demonstrate that PU.1 and Spi-B are essential transcriptional regulators of B-cell differentiation as well as novel tumor suppressors in the B-cell lineage.

scholarly journals Genomic Characterization of Paired Diagnosis and Relapse Samples from Adult Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5281-5281
Author(s):  
Jordi Ribera ◽  
Mar Mallo ◽  
Lurdes Zamora ◽  
Neus Solanes ◽  
Susana Vives ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Normal Karyotype ◽  
Genetic Alterations ◽  
The Other ◽  
Recurrent Event ◽  
Cell Precursor ◽  
Dismal Prognosis

Abstract Background & Objective: Acute Lymphoblastic Leukemia (ALL) is an aggressive neoplasia characterized by a high genetic heterogeneity both at diagnosis and at relapse. Due to the high incidence of relapse in adults and the dismal prognosis beyond recurrence, diagnosis and relapse samples of adult ALL patients were carefully analyzed in order to identify genetic alterations related with drug resistance and disease progression. Patients & Methods: Paired diagnosis-relapse bone marrow samples from 5 adult B-cell precursor ALL (B-ALL) patients were analyzed (Ph+ ALL [n=2], normal karyotype [n=1], t(1;19)(q23;p13) [n=1] and t(8;13)(p21-22;q12) [n=1]). Copy Number Alterations (CNA) were studied with Multiplex Ligation-dependent Probe Amplification (MLPA, kits P-335 and P-202 from MRC-Holland, Amsterdam, Netherlands) and Affymetrix CytoScan HD arrays (Affymetrix, Santa Clara, USA). In the array analyses, only the CNA that encompassed at least 25 markers were considered significant. Results: Regarding karyotype, 2 patients (1 Ph+ and 1 t(1;19) at diagnosis) showed the same chromosomal translocations within a complex karyotype at relapse. On the contrary, the other Ph+ patient showed a normal karyotype at relapse, while 2 patients did not experience any karyotypic change. Regarding immunophenotype, 3/5 patients showed changes on antigen expression from diagnosis to relapse such as expression of markers of immaturity (CD34, TdT positivity and CD38 negativity), loss of lymphoid markers (CD20 and CD22) and/or acquisition of myeloid markers (CD33 and CD66c). Concerning CNA, all relapse samples were genetically related to the diagnosis clone (common clonal origin). All relapsed populations lost CNA detected at diagnosis and/or acquired new CNA but retained some of the CNA showed at diagnosis revealing clonal evolution from ancestral clones. CNA in B-ALL key genes involved in lymphoid development (IKZF1, PAX5, EBF1,VPREB1 and BLNK), proliferation (CDKN2A/B, RB1, CRLF2, C-MYC and ERG), apoptosis (BTG1, TP53 and ATM), hematopoiesis transcription factors (ETV6 and MLL) and histone modifications (KDM6A) were detected, among others. Losses in 9p were the most recurrent event both at diagnosis and at relapse. CDKN2A/B deletions were observed in all relapse samples (3/5 in homozygosis) while PAX5 deletions were present in 4/5 relapsed cases. Interestingly, all relapse samples showed CNA favoring the activation and/or the transcription of proteins involved in the Akt/C-MYC signaling pathway. Another common feature (4/5 patients) were CNA affecting genes involved in drug transport such as several ABC transporter genes and genes related to drug resistance such as PRKDC and RUNX1T1 (in 3/4 of the cases, the CNA appeared exclusively at relapse or were already present at diagnosis and increased their frequency at relapse). CNA in genes that may confer stem cell characteristics (EGR1 and USP16) were another recurrent event at relapse (3/5 samples, 2 of them were not present at diagnosis). CNA affecting the X/Y PAR1 region (CRLF2, CSF2RA and IL3RA) or VPREB1 at 22q11.22 were detected in 3/5 relapse samples, respectively. An important apoptosis cluster at 11q21q24.2 (BIRC2/3, CASP1/4/5/12, hsa-miR-34b/c, ATM and BTG4) was lost in 2/5 relapse samples (one of them was not detected at diagnosis and the other increased its frequency at relapse). Finally, ETV6 deletion (12p13.2) and duplication of Xq26.2q28 (containing ABCD1, BCAP31 and genes coding for several cancer/testis antigens) were observed in 2 relapse samples. Conclusions: SNP arrays analysis of paired B-cell precursor ALL samples at diagnosis and at relapse allows the identification of genetic alterations potentially related with ALL progression. The systematic analysis of relapse samples could contribute to the identification of specific genetic targets with potential therapeutic impact for each patient (personalized medicine). Disclosures Martínez-López: Novartis: Honoraria, Speakers Bureau. Sole:Celgene: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Identification of the Energy Stress Sensor AMPK As Therapeutic Target in Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2771-2771
Author(s):  
Lai N Chan ◽  
Jaewoong Lee ◽  
Kadriye Nehir Cosgun ◽  
Huimin Geng ◽  
Gang Xiao ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Glycolytic Activity ◽  
Novel Therapeutic

Abstract Background and Hypothesis: While often transformed by the same oncogenes, biological and clinical characteristics of B-cell lineage and myeloid leukemias markedly differ. For instance, BCR-ABL1 tyrosine kinase drives both chronic myeloid leukemia (CML) and B cell lineage Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). While the majority of CML patients achieve long-term disease-free survival under treatment, Ph+ ALL patients invariably relapse within months after initial remission. Here, we investigated whether the distinct characteristics of Ph+ ALL and CML have a metabolic basis and identified the metabolic sensor LKB1 and its substrate AMPK as novel therapeutic targets in pre-B ALL. Results: Metabolic measurements revealed strikingly higher AMP:ATP ratios with concomitant decreases in ATP production in patient-derived Ph+ ALL cells when compared to CML cells. These findings indicate a state of chronic energy depletion in pre-B ALL cells. Energy deficit activates the LKB1-AMPK energy sensor pathway to stimulate glucose uptake to restore ATP levels. Notably, LKB1 levels and activity of its substrate AMPKα were higher in patient-derived Ph+ ALL cells compared to CML cells. To study the consequences of inducible deletion of Lkb1, murine BCR-ABL1-driven myeloid lineage (CML) and B cell precursor (Ph+ ALL) Lkb1fl/fl leukemia cells were generated. We found that Lkb1-deletion increased glycolysis, ATP levels and proliferation in myeloid leukemia, consistent with the common notion that LKB1 is an established tumor suppressor. On the contrary, loss of Lkb1 function resulted in diminished glycolytic activity, impaired mitochondrial functions and cell death in pre-B ALL cells. C/EBPa-mediated reprogramming of B-cell into myeloid identity reversed the detrimental effects of Lkb1-deletion, restoring glycolysis, energy levels and survival of B→ myeloid reprogrammed cells. To study Lkb1 early in B cell lineage in vivo, Lkb1fl/fl mice were crossed with Mb1-Cretg/+ mice. Loss of Lkb1 function strikingly eradicated early B cell progenitor cells in vivo. Reduced survival fitness upon Lkb1 deletion in pre-B ALL cells was largely rescued by metabolites that can enter the TCA cycle and thus provide ATP. Importantly, we found that inducible deletion of Lkb1 delayed onset of pre-B ALL and prolonged survival of transplant recipient mice in vivo. Similar to observations made with deletion of Lkb1 in murine BCR-ABL1 pre-B ALL cells, both loss of Ampka function and small molecule inhibition of AMPK (BML-275) resulted in cell death as well as reduced glycolytic activity and mitochondrial function in BCR-ABL1 pre-B ALL cells. Moreover, prolonged overall survival was observed in transplant recipient mice injected with Ampka-deficient pre-B ALL cells. Finally, BML-275 synergized with glucocorticoids, a central component of all main therapy regimen in pre-B ALL, in eradicating patient-derived pre-B ALL cells. Conclusions: Taken together, our findings showed that B-cell lineage leukemia, unlike myeloid leukemia, critically depend on LKB1/AMPK signaling for survival. Our findings also showed that LKB1/AMPK can be leveraged to provide a novel therapeutic avenue in pre-B ALL. Disclosures Hochhaus: BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding.

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