Establishment and characterization of a childhood T-cell acute lymphoblastic leukemia cell line, PER-255, with chromosome abnormalities involving 7q32-34 in association with T-cell receptor- beta gene rearrangement

Abstract A human leukemia cell line, PER-255, was established from the bone marrow of a 5-year-old boy with features typical of lymphomatous T- acute lymphoblastic leukemia (T-ALL). The leukemic origin of cell line PER-255 is indicated by its cytochemical and immunologic similarity to the patient's fresh leukemic cells, which correspond to immature cortical thymocytes. Southern blot analysis showed that the IgJH genes were in germline configuration, whereas both alleles of the T-cell receptor-beta (TCR-beta) gene were rearranged in PER-255 cells, with identical rearrangements present in the patient's leukemic cells. Cytogenetic analysis of the cell line revealed a single abnormal clone with the karyotype 46,XY,t(7;10)(q32–34;q24),t(9;12) (p22;p12–13). Reciprocal translocations involving chromosome bands 7q32–36, containing the gene for the TCR-beta chain, have been reported for a number of tumors of T-cell origin. Translocations involving the 7q32–36 region appear to be nonrandomly associated with childhood T-ALL, whereas abnormalities of 9p and 12p have been reported to be nonrandomly involved in ALL but not specifically associated with the T- cell phenotype.

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Establishment and characterization of a childhood T-cell acute lymphoblastic leukemia cell line, PER-255, with chromosome abnormalities involving 7q32-34 in association with T-cell receptor- beta gene rearrangement

Blood ◽

10.1182/blood.v74.1.369.bloodjournal741369 ◽

1989 ◽

Vol 74 (1) ◽

pp. 369-373

Author(s):

UR Kees ◽

R Lukeis ◽

J Ford ◽

OM Garson

Keyword(s):

T Cell ◽

Cell Line ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

Cell Receptor ◽

Leukemic Cells ◽

Leukemia Cell Line ◽

T Cell Receptor Beta ◽

Beta Gene ◽

Receptor Beta

A human leukemia cell line, PER-255, was established from the bone marrow of a 5-year-old boy with features typical of lymphomatous T- acute lymphoblastic leukemia (T-ALL). The leukemic origin of cell line PER-255 is indicated by its cytochemical and immunologic similarity to the patient's fresh leukemic cells, which correspond to immature cortical thymocytes. Southern blot analysis showed that the IgJH genes were in germline configuration, whereas both alleles of the T-cell receptor-beta (TCR-beta) gene were rearranged in PER-255 cells, with identical rearrangements present in the patient's leukemic cells. Cytogenetic analysis of the cell line revealed a single abnormal clone with the karyotype 46,XY,t(7;10)(q32–34;q24),t(9;12) (p22;p12–13). Reciprocal translocations involving chromosome bands 7q32–36, containing the gene for the TCR-beta chain, have been reported for a number of tumors of T-cell origin. Translocations involving the 7q32–36 region appear to be nonrandomly associated with childhood T-ALL, whereas abnormalities of 9p and 12p have been reported to be nonrandomly involved in ALL but not specifically associated with the T- cell phenotype.

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Establishment of a NOD/SCID/γc−/−-Dependent Lymphoid Leukemia Cell Line, D593, with Novel RUNX1-LAF4 Fusion Gene.

Blood ◽

10.1182/blood.v108.11.4276.4276 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4276-4276

Author(s):

Akihiro Abe ◽

Manabu Ninomiya ◽

Shizuka Imagama ◽

Momoko Suzuki ◽

Fumihiko Hayakawa ◽

...

Keyword(s):

T Cell ◽

Cell Line ◽

Fusion Gene ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

Cell Receptor ◽

Leukemia Cell Line ◽

Leukemia Cells ◽

Pcr Analysis ◽

Lymphoid Leukemia

Abstract We established a NOD/SCID/γc−/−(NOG mouse)-dependent human lymphoid leukemia cell line, D593, by repeated xenotransplantation of pediatric T-cell acute lymphoblastic leukemia cells with the translocation t(2;21). The cell line, D-593, could be serially transplanted from mouse to mouse over a 2-year period. D593 had the same immuno-phenotype as the original leukemia cells: positive for CD2, 5, 7, 14, and 34, and negative for CD3, 4, 8, 19, and 41a. Cytoplasmic CD3 was positive and the rearrangement of T-cell receptor was detected by Southern blot analysis. A previously unreported translocation of t(2;21)(q11;q22) was observed in both the original patient sample and D593. The split signal of RUNX1 was detected by fluorescence in site hybridization in D593 indicating the involvement of RUNX1. Using 3′-RACE and RT-PCR analysis, we identified novel chimeric transcripts of RUNX1-LAF4 joining exon 7 of RUNX1 to exon 4 of LAF4. In the transplanted NOG mice, D593 homed into the trabecular endosteal region of bone marrow (BM), and proliferated from the endosteum to medulla. At the late stage of engraftment, the BM was filled with human lymphoblasts and metastases into the trabecular of the spleen and Glisson’s sheath of the liver were also observed. These findings suggest that D593 is a useful cell line to study not only the leukemia-related biology of RUNX1-LAF4 but also the novel therapeutic model against core-binding factor (CBF) leukemia.

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Digoxin-Like Immunoreactive Factors Induce Apoptosis in Human Acute T-Cell Lymphoblastic Leukemia

Clinical Chemistry ◽

10.1373/clinchem.2006.082081 ◽

2007 ◽

Vol 53 (7) ◽

pp. 1315-1322 ◽

Cited By ~ 19

Author(s):

Kenneth Ihenetu ◽

Hassan M Qazzaz ◽

Fabian Crespo ◽

Rafael Fernandez-Botran ◽

Roland Valdes

Keyword(s):

T Cell ◽

Cell Line ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

Jurkat Cells ◽

Leukemic Cells ◽

Leukemia Cell Line ◽

Induction Of Apoptosis ◽

K 562 Cells ◽

Induced Apoptosis

Abstract Background: Plant-derived cardenolides reportedly possess anticancer properties in human leukemic cells via selective induction of apoptosis, cell cycle arrest, and differentiation. Selective induction of apoptosis with mammalian-derived digoxin-like immunoreactive factor (DLIF) could provide new strategies for anticancer drug development or the identification of biomarkers for cancer. We investigated whether DLIFs selectively induce apoptosis in human lymphoblastic leukemic cells. Methods: We compared the relative potencies of digoxin, ouabain, and DLIF on induction of programmed cell death in Jurkat cells (an acute T-leukemic cell line), K-562 (a myelogenous leukemia cell line), and nonpathologic human peripheral blood mononuclear cells (PBMCs). Apoptosis was measured by flow cytometry with the annexin V/propidium iodide method. Results: Digoxin and ouabain induced apoptosis in Jurkat cells [digoxin 50% inhibitory concentration (IC50), 24 nmol/L; ouabain IC50, 26 nmol/L]. Neither digoxin nor ouabain induced apoptosis in K-562 cells or PBMCs. DLIF was more potent (IC50, 1.9 nmol/L) and >2-fold more effective than digoxin or ouabain at inducing maximum apoptosis in Jurkat cells. The IC50 values in the apoptosis assays were >100-fold lower (DLIF) and 20-fold lower (digoxin and ouabain) than the IC50 required for Na+- and K+-dependent ATPase (DLIF, 200 nmol/L; digoxin, 910 nmol/L; ouabain, 600 nmol/L). Conclusion: DLIF selectively induces apoptosis in a human acute T-cell lymphoblastic leukemia cell line but not in K-562 cells or PBMCs. These data suggest a new physiological role for these endogenous hormone-like factors.

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Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics

Blood ◽

10.1182/blood.v65.1.21.21 ◽

1985 ◽

Vol 65 (1) ◽

pp. 21-31 ◽

Cited By ~ 194

Author(s):

RC Stong ◽

SJ Korsmeyer ◽

JL Parkin ◽

DC Arthur ◽

JH Kersey

Keyword(s):

Acute Leukemia ◽

Cell Line ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

Leukemic Cells ◽

Leukemia Cell Line ◽

Terminal Deoxynucleotidyl Transferase ◽

Immunoglobulin Gene ◽

A Cell ◽

B Lineage

Abstract A cell line, designated RS4;11, was established from the bone marrow of a patient in relapse with an acute leukemia that was characterized by the t(4;11) chromosomal abnormality. The cell line and the patient's fresh leukemic cells both had the t(4;11)(q21;q23) and an isochromosome for the long arm of No. 7. Morphologically, all cells were lymphoid in appearance. Ultrastructurally and cytochemically, approximately 30% of the cells possessed myeloid features. The cells were strongly positive for terminal deoxynucleotidyl transferase. They were HLA-DR positive and expressed surface antigens characteristic for B lineage cells, including those detected by anti-B4, BA-1, BA-2, and PI153/3. Immunoglobulin gene analysis revealed rearrangements of the heavy chain and kappa chain genes. The cells lacked the common acute lymphoblastic leukemia antigen and antigenic markers characteristic of T lineage cells. The cells reacted with the myeloid antibody 1G10 but not with other myeloid monoclonal antibodies. Treatment with 12-O-tetradecanoyl- phorbol-13-acetate induced a monocyte-like phenotype demonstrated by cytochemical, functional, immunologic, and electron microscopic studies. The expression of markers of both early lymphoid and early myeloid cells represents an unusual phenotype and suggests that RS4;11 represents a cell with dual lineage capabilities. To our knowledge, RS4;11 is the first cell line established from t(4;11)-associated acute leukemia.

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Establishment and characteristics of a T-cell acute lymphoblastic leukemia cell line, JK-T1, with a chromosomal translocation between 8q24 and 14q13

Cancer Genetics and Cytogenetics ◽

10.1016/0165-4608(92)90329-7 ◽

1992 ◽

Vol 64 (1) ◽

pp. 86-90 ◽

Cited By ~ 6

Author(s):

Mitsuyoshi Urashima ◽

Hideaki Iyori ◽

Kouji Fujisawa ◽

Yasutaka Hoshi ◽

Jun-ichi Akatsuka ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Cell Line ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

Chromosomal Translocation ◽

Leukemia Cell Line ◽

Cell Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia Cell Line

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Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v70.6.1933.bloodjournal7061933 ◽

1987 ◽

Vol 70 (6) ◽

pp. 1933-1939

Author(s):

A Tawa ◽

SH Benedict ◽

J Hara ◽

N Hozumi ◽

EW Gelfand

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

T Cell Receptor ◽

Gene Rearrangement ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

Cell Receptor ◽

Gene Rearrangements ◽

Gamma Chain ◽

Beta Gene

We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.

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Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines

Blood ◽

10.1182/blood.v68.5.1101.bloodjournal6851101 ◽

1986 ◽

Vol 68 (5) ◽

pp. 1101-1107 ◽

Cited By ~ 1

Author(s):

AJ Furley ◽

BR Reeves ◽

S Mizutani ◽

LJ Altass ◽

SM Watt ◽

...

Keyword(s):

T Cell ◽

Cell Line ◽

Myeloid Cell ◽

Cell Receptor ◽

High Level Expression ◽

Igh Genes ◽

T Cell Receptor Beta ◽

Molecular Phenotypes ◽

High Level ◽

Receptor Beta

The cell line KG1 derived from a patient with erythroleukemia in myeloblastic relapse has the composite phenotype and functional repertoire of myeloblasts. In marked contrast, its subline KG1a has lost myeloid features, acquired new karyotypic markers, and has three characteristics associated with immature T cells: low-level expression of the T cell receptor beta mRNA (but not alpha) transcribed from a germline gene; high-level expression of T3 delta mRNA and intracellular, but not cell surface, T3 protein; and expression of the CD7/gp40 T cell-associated membrane antigen. Both KG1 and KG1a transcribe unrearranged IgH genes. These data suggest that either the KG1 cell line was derived from a common myeloid-lymphoid progenitor or that the KG1a subline phenotype is aberrant.

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Terminal deoxynucleotidyl transferase expression can precede T cell receptor beta chain and gamma chain rearrangement in T cell acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v69.1.356.bloodjournal691356 ◽

1987 ◽

Vol 69 (1) ◽

pp. 356-360

Author(s):

JM Greenberg ◽

JH Kersey

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

T Cell Receptor ◽

Lymphoblastic Leukemia ◽

Cell Receptor ◽

Terminal Deoxynucleotidyl Transferase ◽

Beta Chain ◽

Gamma Chain ◽

T Cell Receptor Beta ◽

Receptor Beta

The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is thought to contribute to the diversity of certain immunoglobulin and T cell receptor gene rearrangements through the addition of random nucleotides at their variable (V)-joining (J) region junctions. An acute lymphoblastic leukemia (ALL) with an immature T cell phenotype (CD7+, CD5+, CD1+/-, CD2+/-, CD3-, CD4-, CD8-) was found to be TdT+ with germline immunoglobulin heavy chain, T cell receptor beta chain, and T cell gamma chain genes. The data indicate that TdT expression can precede T gamma and T beta rearrangement during T lymphoid ontogeny consistent with its proposed association with the T cell receptor rearrangement process. Southern analysis of certain cases of T-ALL may not result in the detection of a monoclonal population of cells.

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