scholarly journals Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact

2021 ◽  
Vol 11 ◽  
Author(s):  
Till Braun ◽  
Annika Dechow ◽  
Gregor Friedrich ◽  
Michael Seifert ◽  
Johanna Stachelscheid ◽  
...  
Keyword(s):  
T Cell ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Disease Model ◽  
Cell Receptor ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Prolymphocytic Leukemia ◽  
Tcr Signals ◽  
Family Based

T-cell prolymphocytic leukemia (T-PLL) is the most common mature T-cell leukemia. It is a typically aggressively growing and chemotherapy-resistant malignancy with a poor prognosis. T-PLL cells resemble activated, post-thymic T-lymphocytes with memory-type effector functions. Constitutive transcriptional activation of genes of the T-cell leukemia 1 (TCL1) family based on genomic inversions/translocations is recognized as a key event in T-PLL’s pathogenesis. TCL1’s multiple effector pathways include the enhancement of T-cell receptor (TCR) signals. New molecular dependencies around responses to DNA damage, including repair and apoptosis regulation, as well as alterations of cytokine and non-TCR activation signaling were identified as perturbed hallmark pathways within the past years. We currently witness these vulnerabilities to be interrogated in first pre-clinical concepts and initial clinical testing in relapsed/refractory T-PLL patients. We summarize here the current knowledge on the molecular understanding of T-PLL’s pathobiology and critically assess the true translational progress around this to help appraisal by caregivers and patients. Overall, the contemporary concepts on T-PLL’s pathobiology are condensed in a comprehensive mechanistic disease model and promising interventional strategies derived from it are highlighted.

scholarly journals Cytogenetic studies on prolymphocytic leukemia. II. T cell prolymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 926-931 ◽  
Author(s):  
V Brito-Babapulle ◽  
M Pomfret ◽  
E Matutes ◽  
D Catovsky
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Partial Trisomy ◽  
Cell Receptor ◽  
Chain Gene ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Prolymphocytic Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

We report chromosome abnormalities in 15 cases of T cell prolymphocytic leukemia (T-PLL). All cases were characterized by clinical, morphological, and membrane marker analysis. The most frequent abnormality was an inv(14)(q11q32) observed in nine cases. The T cell receptor (TCR) alpha chain gene is localized to 14q11 and the immunoglobulin heavy-chain gene to region 14q32. Four cases also had translocations involving 14q11. Trisomy or multisomy for 8q resulting from an i(8q) or from rearrangements with 8p12 as the breakpoint was observed in nine cases, and a deletion of 6q was found in four cases. Trisomy or partial trisomy for 7q was observed in four cases, of which two had abnormalities of band 7q35 to which the TCR beta chain gene is mapped. The expression of Tac antigen, investigated in 27 cases of human T cell leukemia virus I-negative chronic T cell leukemia, which included the 15 cases of T-PLL, showed a good correlation with abnormalities of 7q35. Our studies on chronic T leukemias suggest that inv(14)(q11q32) and trisomy for 8q are abnormalities characteristic of T-PLL.

scholarly journals Cytogenetic studies on prolymphocytic leukemia. II. T cell prolymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 926-931 ◽  
Author(s):  
V Brito-Babapulle ◽  
M Pomfret ◽  
E Matutes ◽  
D Catovsky
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Partial Trisomy ◽  
Cell Receptor ◽  
Chain Gene ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Prolymphocytic Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Abstract We report chromosome abnormalities in 15 cases of T cell prolymphocytic leukemia (T-PLL). All cases were characterized by clinical, morphological, and membrane marker analysis. The most frequent abnormality was an inv(14)(q11q32) observed in nine cases. The T cell receptor (TCR) alpha chain gene is localized to 14q11 and the immunoglobulin heavy-chain gene to region 14q32. Four cases also had translocations involving 14q11. Trisomy or multisomy for 8q resulting from an i(8q) or from rearrangements with 8p12 as the breakpoint was observed in nine cases, and a deletion of 6q was found in four cases. Trisomy or partial trisomy for 7q was observed in four cases, of which two had abnormalities of band 7q35 to which the TCR beta chain gene is mapped. The expression of Tac antigen, investigated in 27 cases of human T cell leukemia virus I-negative chronic T cell leukemia, which included the 15 cases of T-PLL, showed a good correlation with abnormalities of 7q35. Our studies on chronic T leukemias suggest that inv(14)(q11q32) and trisomy for 8q are abnormalities characteristic of T-PLL.

T-cell receptor γδ T-cell leukemia with the morphology of T-cell prolymphocytic leukemia and a postthymic immunophenotype

2001 ◽  
Vol 80 (12) ◽  
pp. 749-751 ◽  
Author(s):  
T. Sugimoto ◽  
S. Imoto ◽  
Y. Matsuo ◽  
K. Kojima ◽  
M. Yasukawa ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Leukemia ◽  
Γδ T Cell ◽  
Cell Leukemia ◽  
Prolymphocytic Leukemia

scholarly journals T-cell receptor chain Vbeta subunit staining to quantify the malignant clone in adult T-cell leukemia

Retrovirology ◽  
2015 ◽  
Vol 12 (S1) ◽  
Author(s):  
Aileen G Rowan ◽  
Paul Fields ◽  
Graham P Taylor ◽  
Charles RM Bangham
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Receptor Chain

scholarly journals S-100 beta positive T cell leukemia

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1299-1303
Author(s):  
K Takahashi ◽  
Y Ohtsuki ◽  
H Sonobe ◽  
K Hayashi ◽  
S Nakamura ◽  
...  
Keyword(s):  
T Cell ◽  
Human Peripheral Blood ◽  
Leukemic Cell ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
S 100 ◽  
T Cell Phenotypes

We reported a peculiar case with T cell leukemia. The patient was a 34- year-old woman showing extensive splenomegaly and marked leukemic cell proliferation and running a rapid fatal clinical course. The leukemic cells were morphologically ordinary lymphocytes showing suppressor/cytotoxic(s/c) T cell phenotypes and containing S-100b protein. Southern blot analysis revealed rearrangement of the beta chain genes of the T cell receptor (TcR) of the leukemic cells. Because these phenotypic and morphologic features were identical with those of S-100 beta+T lymphocytes (S-100 beta +TL) in normal human peripheral blood, we regarded this case as S-100 beta +T cell leukemia. We discussed clinicopathological features of S-100 beta +T cell leukemia/lymphoma by assessing similar cases reported so far. S-100 beta +T cell leukemia/lymphoma is a new type of s/c T lymphocytic leukemia/lymphoma with aggressive features.

scholarly journals T Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells

2016 ◽  
Vol 12 (11) ◽  
pp. e1006030 ◽  
Author(s):  
Aileen G. Rowan ◽  
Aviva Witkover ◽  
Anat Melamed ◽  
Yuetsu Tanaka ◽  
Lucy B. M. Cook ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Cell Receptor ◽  
Leukemia Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
T Cell Receptor Vβ

scholarly journals S-100 beta positive T cell leukemia

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1299-1303 ◽  
Author(s):  
K Takahashi ◽  
Y Ohtsuki ◽  
H Sonobe ◽  
K Hayashi ◽  
S Nakamura ◽  
...  
Keyword(s):  
T Cell ◽  
Human Peripheral Blood ◽  
Leukemic Cell ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
S 100 ◽  
T Cell Phenotypes

Abstract We reported a peculiar case with T cell leukemia. The patient was a 34- year-old woman showing extensive splenomegaly and marked leukemic cell proliferation and running a rapid fatal clinical course. The leukemic cells were morphologically ordinary lymphocytes showing suppressor/cytotoxic(s/c) T cell phenotypes and containing S-100b protein. Southern blot analysis revealed rearrangement of the beta chain genes of the T cell receptor (TcR) of the leukemic cells. Because these phenotypic and morphologic features were identical with those of S-100 beta+T lymphocytes (S-100 beta +TL) in normal human peripheral blood, we regarded this case as S-100 beta +T cell leukemia. We discussed clinicopathological features of S-100 beta +T cell leukemia/lymphoma by assessing similar cases reported so far. S-100 beta +T cell leukemia/lymphoma is a new type of s/c T lymphocytic leukemia/lymphoma with aggressive features.

scholarly journals Leukopenic chronic T cell leukemia mimicking hairy cell leukemia: association with human retroviruses

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 949-956 ◽  
Author(s):  
CC Sohn ◽  
DW Blayney ◽  
JL Misset ◽  
G Mathe ◽  
G Flandrin ◽  
...  
Keyword(s):  
T Cell ◽  
Hairy Cell Leukemia ◽  
Sheep Erythrocyte ◽  
The Other ◽  
Leukemic Cells ◽  
Type I ◽  
T Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Prolymphocytic Leukemia

Abstract We report two cases of a T cell lymphoproliferative disease not previously described, with cytologic and clinical features similar to those associated with Galton's “prolymphocytic” leukemia (PL). Our patients, like those with Galton's PL, had massive splenomegaly and minimal or absent hepatomegaly and lymphadenopathy. In contrast, however, our patients had leukopenia, as well as low percentages of leukemic cells in the peripheral blood and in the bone marrow. In splenic imprints, the nuclear chromatin pattern of most of the leukemic cells was intermediate between those of mature lymphocytes and those of lymphoblasts, and the nuclei contained single, centrally located, conspicuous nucleoli. In sections of the spleen, the leukemic cells diffusely infiltrated the red pulp in a pattern strikingly similar to that of hairy cell leukemia; however, when the leukemic cells were studied cytochemically, the cytoplasmic acid phosphatase positivity was punctate and tartrate-sensitive. The leukemic cells were sheep erythrocyte rosette-positive and expressed T cell-associated antigens. Initially, both patients responded well to therapeutic splenectomy. One patient received combination chemotherapy after splenectomy and is alive and well 24 months after diagnosis. The other patient was in complete clinical remission for one year after splenectomy and received chemotherapy at relapse. He died, however, 23 months after splenectomy, with disseminated disease. IgG antibody titers against human T lymphotropic virus type I (HTLV-I) were detected in one patient and against HTLV-II in the other. The leukemia in these patients represents a distinct clinicopathologic entity within the spectrum of peripheral T cell lymphoproliferative diseases that includes Galton's PL of T cell derivation, T cell chronic lymphocytic leukemia, T cell hairy cell leukemia, and adult T cell leukemia/lymphoma.

scholarly journals Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling

Blood ◽  
2006 ◽  
Vol 108 (1) ◽  
pp. 305-310 ◽  
Author(s):  
Antonio F. Campese ◽  
Annette I. Garbe ◽  
Fangrong Zhang ◽  
Fabio Grassi ◽  
Isabella Screpanti ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Models ◽  
Disease Development ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Malignant Growth ◽  
Tcr Signaling ◽  
Tcr Signals

Overexpression of intracellular Notch plays an important role in the generation of human acute lymphoblastic T cell leukemia (T-ALL). In mouse models, it was shown that Notch-dependent T-ALL required pre-TCR signaling. Here we show that pre-TCR signaling is required to condition mice for Notch-dependent transformation but that it is not required to sustain malignant growth of T-ALL. In contrast to previous studies, we found that disease development does not require pre-TCR but that it can be accelerated in Rag2-/- mice by transient mimicking of pre-TCR signals. (Blood. 2006;108:305-310)

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