Detection of identical Hodgkin–Reed Sternberg cell specific immunoglobulin gene rearrangements in a patient with Hodgkin’s disease of mixed cellularity subtype at primary diagnosis and in relapse two and a half years later

Jox, Andrea; Zander, Thomas; Kornacker, Martin; Kanzler, Holger; Küppers, Ralf; Diehl, Volker; Wolf, Jürgen

doi:10.1023/a:1008249214328

Cited by 22 publications

(4 citation statements)

References 19 publications

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“…Thus, PET obviously is able to detect emerging relapses some months before they can be displayed by CT scan, but, for technical reasons, the resolution of PET is presumably not good enough to detect minimal residual disease, which can cause late relapses (Ͼ 12 months) in HL. 15 Thus, a negative PET should predict PFS for at least 12 months in most cases.…”

Section: Response and Fdg-pet In Hodgkin Lymphoma 3991mentioning

confidence: 99%

Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma

Kobe

Dietlein

Franklin

et al. 2008

Blood

200

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In the HD15 trial of the German Hodgkin Study Group, the negative predictive value (NPV) of positron emission tomography (PET) using [ 18 F]-fluorodeoxyglucose in advanced-stage Hodgkin lymphoma (HL) was evaluated. A total of 817 patients were enrolled and randomly assigned to receive BEACOPP-based chemotherapy. After completion of chemotherapy, residual disease measuring more than or equal to 2.5 cm in diameter was assessed by PET in 311 patients. The NPV of PET was defined as the proportion of PET ؊ patients without progression, relapse, or irradiation within 12 months after PET review panel. The progression-free survival was 96% for PET ؊ patients (95% confidence interval [CI], 94%-99%) and 86% for PET ؉ patients (95% CI, 78%-95%, P ‫؍‬ .011). The NPV for PET in this analysis was 94% (95% CI, 91%-97%). Thus, consolidation radiotherapy can be omitted in PET ؊ patients with residual disease without increasing the risk for progression or early relapse compared with patients in complete remission. The impact of this finding on the overall survival at 5 years must be awaited. Until then, response adapted therapy guided by PET for HL patients seems to be a promising approach that should be further evaluated in clinical trials. This trial is registered at http://isrctn.org study as #IS-RCTN32443041.(Blood. 2008;112: 3989-3994)

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Section: Response and Fdg-pet In Hodgkin Lymphoma 3991mentioning

confidence: 99%

Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma

Kobe

Dietlein

Franklin

et al. 2008

Blood

200

View full text Add to dashboard Cite

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“…Instead, they survive, clonally expand, and lead to disseminated tumor growth and clonal relapse. 25,26 Several studies have shown CD95/Fas expression by HRS cells. 27,28 However, cultured HRS cells are resistant to Fas-mediated apoptosis.…”

mentioning

confidence: 99%

Constitutive Expression of c-FLIP in Hodgkin and Reed-Sternberg Cells

Thomas

Kallenborn

Wickenhauser

et al. 2002

The American Journal of Pathology

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Crosslinking of the transmembrane receptor CD95/ Fas leads to activation of a signaling cascade resulting in apoptosis. c-FLIP is a recently described protein that potently inhibitsCD95/Fas protein is a 45-kd transmembrane protein that belongs to the tumor necrosis factor superfamily type of receptors.1 Crosslinking of the receptor leads to the clustering of an oligomolecular signaling platform, termed death-inducing signaling complex (DISC) that consists of the death domain of the intracellular part of Fas, the adapter molecule Fas-associated-death domain, and the cysteine protease caspase-8. Autoproteolytical cleavage of caspase-8 at the DISC leads to activation of the caspase cascade resulting in the cleavage of DNA and finally, cell death.2,3 CD95/Fas plays a critical role in the elimination of autoreactive T and B cells and inactivation of Fas by mutation or deletion in humans results in the production of autoreactive antibodies, accumulation of activated lymphocytes, splenomegaly, and a high risk for the development of B cell neoplasms. 4 -6

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“…The bone marrow cells (BMC) of the same patient whose peripheral blood cells were used to establish the cell line L1236, were harvested for autologous bone marrow transplantation during complete clinical remission (for case report of the patient see Jox et al (1998) and used as normal tissue control for determination of the patient's germ line allelotype.…”

Section: Bone Marrow Cellsmentioning

confidence: 99%

“…Therefore, the patient's bone marrow cells (BMC), which were obtained during complete clinical remission, were analysed to exclude minimal residual disease. The V H 1 gene rearrangement of L1236 cells was already used to detect the patient's H-RS cells in various tissues obtained during the course of the disease (Jox et al, 1998). To test the patient's BMC for the presence of H-RS cells a seminested PCR was performed.…”

Section: Analysis Of the Patient's Bone Marrow Cells For Minimal Resimentioning

confidence: 99%

Loss of heterozygosity in the Hodgkin-Reed Sternberg cell line L1236

et al. 2001

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Summary Hodgkin-Reed Sternberg cells are derived from germinal centre B-cells in most cases. Somatic mutations affecting their rearranged immunoglobulin genes were detected, rendering potential functional rearrangements non-functional. Under physiological conditions such cells would be designated to undergo apoptosis within the germinal centre. In search for the specific transforming event that prevents Hodgkin-Reed Sternberg cells from programmed cell death, cytogenetic analyses were broadly performed but did not reveal specific chromosomal aberrations. Analysis of these cells on the molecular level is difficult to perform due to the scarcity of the cells in the lymphoma tissue and the given limitations of in situ studies. To overcome these limitations, the cell line L1236, known to be derived from Hodgkin-Reed Sternberg cells in situ, was chosen for allelotype analysis. Using a panel of microsatellite loci assigned to nearly all chromosomal arms, regions of loss of heterozygosity were detected on chromosomal arms 6p, 9q and 17p. The size of lost segments was estimated by amplification of additional microsatellite loci mapped to the respective regions. Further analyses of single Hodgkin-Reed Sternberg cells will reveal whether LOH affecting these regions is a recurrent event in HD and to which extent the smallest commonly affected region can be estimated.

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Detection of identical Hodgkin–Reed Sternberg cell specific immunoglobulin gene rearrangements in a patient with Hodgkin’s disease of mixed cellularity subtype at primary diagnosis and in relapse two and a half years later

Cited by 22 publications

References 19 publications

Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma

Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma

Constitutive Expression of c-FLIP in Hodgkin and Reed-Sternberg Cells

Loss of heterozygosity in the Hodgkin-Reed Sternberg cell line L1236

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