scholarly journals Acute lymphoblastic leukemia and non-Hodgkin's lymphoma of T lineage: colony-forming cells retain growth factor (interleukin 2) dependence

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1088-1094 ◽  
Author(s):  
I Touw ◽  
R Delwel ◽  
G van Zanen ◽  
B Lowenberg
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hodgkin’S Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Surface Membrane ◽  
Interleukin 2 ◽  
Receptor Activation ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract The regulatory role of interleukin 2 (IL 2) in the proliferation of T acute lymphoblastic leukemia (T-ALL) and T non-Hodgkin's lymphoma (T- NHL) cells from six individual patients was analyzed in a colony culture system to which pure recombinant IL 2, and the lectin phytohemagglutinin (PHA) or the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA), had been added. The proliferative response was correlated with the inducibility of receptors for IL 2 on the surface membrane of T-ALL and T-NHL cells by incubation with TPA or PHA for 18 hours. Leukemic T cell colonies, identified by immunophenotyping or cytogenetic analysis, appeared in vitro following TPA and IL 2 stimulation in all six cases. Accordingly, receptors for IL 2, initially absent from the cell surface, were found on high proportions of the T-ALL and T-NHL cells after in vitro exposure to TPA. In contrast, colony formation stimulated by PHA and the induction of IL 2 receptors by PHA were limited to the one case of T-NHL with the mature thymocyte immunophenotype. The cells from the other patients, expressing common or prothymocyte phenotypes, did not respond to PHA. No colonies were formed in any of these cases when PHA or TPA was withheld from the IL 2-containing cultures. Although colony growth depended absolutely on exogenous IL 2 in three cases (ALL), in the three other cases (one ALL, two NHL) some colonies grew also when no IL 2 had been added to the cultures. Upon further analysis of the cells of one of the latter patients, it was found that the cells produced IL 2 and proliferated in response to this endogenous IL 2. The results from this study indicate that the requirements of endogenous v exogenous IL 2 for cell proliferation in T-ALL and T-NHL and IL 2 receptor activation by PHA and TPA vary from patient to patient. In addition, they support the notion that T-ALL and T-NHL cells have not lost dependence on IL 2 and IL 2 receptor activation for in vitro growth.

scholarly journals Acute lymphoblastic leukemia and non-Hodgkin's lymphoma of T lineage: colony-forming cells retain growth factor (interleukin 2) dependence

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1088-1094
Author(s):  
I Touw ◽  
R Delwel ◽  
G van Zanen ◽  
B Lowenberg
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hodgkin’S Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Surface Membrane ◽  
Interleukin 2 ◽  
Receptor Activation ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

The regulatory role of interleukin 2 (IL 2) in the proliferation of T acute lymphoblastic leukemia (T-ALL) and T non-Hodgkin's lymphoma (T- NHL) cells from six individual patients was analyzed in a colony culture system to which pure recombinant IL 2, and the lectin phytohemagglutinin (PHA) or the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA), had been added. The proliferative response was correlated with the inducibility of receptors for IL 2 on the surface membrane of T-ALL and T-NHL cells by incubation with TPA or PHA for 18 hours. Leukemic T cell colonies, identified by immunophenotyping or cytogenetic analysis, appeared in vitro following TPA and IL 2 stimulation in all six cases. Accordingly, receptors for IL 2, initially absent from the cell surface, were found on high proportions of the T-ALL and T-NHL cells after in vitro exposure to TPA. In contrast, colony formation stimulated by PHA and the induction of IL 2 receptors by PHA were limited to the one case of T-NHL with the mature thymocyte immunophenotype. The cells from the other patients, expressing common or prothymocyte phenotypes, did not respond to PHA. No colonies were formed in any of these cases when PHA or TPA was withheld from the IL 2-containing cultures. Although colony growth depended absolutely on exogenous IL 2 in three cases (ALL), in the three other cases (one ALL, two NHL) some colonies grew also when no IL 2 had been added to the cultures. Upon further analysis of the cells of one of the latter patients, it was found that the cells produced IL 2 and proliferated in response to this endogenous IL 2. The results from this study indicate that the requirements of endogenous v exogenous IL 2 for cell proliferation in T-ALL and T-NHL and IL 2 receptor activation by PHA and TPA vary from patient to patient. In addition, they support the notion that T-ALL and T-NHL cells have not lost dependence on IL 2 and IL 2 receptor activation for in vitro growth.

Testicular Disease in Childhood B-Cell Non-Hodgkin’s Lymphoma: The French Society of Pediatric Oncology Experience

2001 ◽  
Vol 19 (9) ◽  
pp. 2397-2403 ◽  
Author(s):  
Jean-Hugues Dalle ◽  
Françoise Mechinaud ◽  
Jean Michon ◽  
Jean-Claude Gentet ◽  
Lionel de Lumley ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Pediatric Oncology ◽  
Hodgkin’S Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Hodgkin's Lymphoma ◽  
French Society ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Testicular Disease

PURPOSE: To investigate whether testicular disease in childhood B-cell lymphoma should continue to be considered a sanctuary site, as it is with other lymphoid malignancies such as acute lymphoblastic leukemia. PATIENTS AND METHODS: Seven hundred forty-two children with B-cell non-Hodgkin’s lymphoma were included in the LMB protocols of the French Society of Pediatric Oncology from February 1981 to May 1994. Thirty patients (5.3%) had testicular involvement at diagnosis. We describe the clinical presentation and outcome of these 30 patients, who were treated without local radiation therapy. RESULTS: Five patients underwent diagnostic orchidectomy. The median patient age was 8.5 years (range, 2 to 14 years), and their cancers were stage III (18 patients), stage IV (five patients), and B-cell acute lymphoblastic leukemia (seven patients). Five patients had central nervous system involvement. Twenty-eight patients (95%) achieved complete remission. Twenty-six patients are alive without progressive disease (median follow-up, 6.5 years). CONCLUSION: Testicular disease does not seem to confer a poor prognosis, and it is curable with intensive combination chemotherapy alone. Local treatment (surgery or radiation) is avoidable; therefore, gonadal function can be preserved.

Non Hodgkin’s lymphoma seven years following remission of acute lymphoblastic leukemia

2004 ◽  
Vol 71 (5) ◽  
pp. 431-432 ◽  
Author(s):  
Sameer Bakhshi ◽  
Paresh Jain ◽  
Mona Anand ◽  
K. Padmanjali ◽  
Rajive Kumar ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hodgkin’S Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

CDC4 and NOTCH1 Mutations in Childhood T-Cell Acute Lymphoblastic Leukemia and T Cell Non-Hodgkin’s Lymphoma; a Japan Association of Childhood Leukemia Study Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2648-2648
Author(s):  
Myoung-ja Park ◽  
Tomohiko Taki ◽  
Nobuhiro Suzuki ◽  
Megumi Oda ◽  
Keiko Yagi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Lines ◽  
Hodgkin’S Lymphoma ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Notch1 Mutations

Abstract Risk-adapted therapy has resulted in a improvement of outcome in childhood acute lymphoblastic leukemia (ALL), however, T-cell ALL (T-ALL) have still relatively poor outcome compared to B-precursor ALL. Although activating mutations of the NOTCH1 gene have been reported in more than half of T-ALL, the prognostic significance of this finding has yet to be determined. CDC4 gene was isolated as a negative regulator of NOTCH1 and mutations were detected in T-ALL cell line and other cancers. We performed mutation analysis of the NOTCH1 and CDC4 gene in 14 T-ALL cell lines, 52 T-ALL and 17 T cell non-Hodgkin’s lymphoma (T-NHL) fresh samples. All children with T-ALL and T-NHL were treated on Japan Association of Childhood Leukemia Study (JACLS) ALL-97 and NHL-98 protocol after obtaining informed consent. Mutation detection was performed via PCR based denaturing HPLC followed by direct sequence.Mutations of the NOTCH1 were identified in 10 (71.4%) of 14 T-ALL cell lines, 16 (30.8%) of 52 T-ALL and 6 (35.3%) of 17 T-NHL fresh samples. Twelve mutations in heterodimerization domain (HD) and 12 mutations in PEST domain (PD) were found in 69 fresh samples. The incidence of the NOTCH1 mutation is less frequent than that of previous reports. We found CDC4 mutations in 12 (35.3%) of 52 T-ALL and 2 (11.8%) of 17 T-NHL fresh samples. One insertion mutation in exon 3 and 11 missense mutations were detected in CDC4 gene. Both NOTCH1 and CDC4 mutations were found in 7 patients. Interestingly, the NOTCH1 mutations were only observed in T-ALL and T-NHL patients without relapse, suggesting to be associated with favorable prognosis. However, CDC4 gene was found not to be associated with prognosis.

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