The persistence of t(14;18)-bearing cells in lymph nodes of patients with follicular lymphoma in complete remission: the evidence for ‘a lymphoma stem cell’

Janíková, Andrea; Mayer, Jiřı́; Křen, Leoš; Šmardová, Jana; Dvořáková, Dana; Neubauer, Jiří; Vášová, Ingrid

doi:10.1080/10428190902927005

Cited by 8 publications

(4 citation statements)

References 33 publications

(33 reference statements)

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“…Because the majority of FL patients with advanced stage disease relapse following diagnosis due to the persistence of residual disease, FISH and/or PCR-detected IgH/bcl-2 rearrangement may be related to the original FL clone developed and detected during follow-up of these patients. Molecular-based studies have shown that t(14;18)-bearing cells may persist in the lymph nodes of FL patients that are in complete remission [27]. Additionally, PCR-based techniques can also detect the MBR/JH fusion sequence in the blood and lymphoid tissues of healthy individuals [28,29].…”

Section: Discussionmentioning

confidence: 99%

MOLECULAR EVALUATION OF t(14;18)(bcl-2/IgH) TRANSLOCATION IN FOLLICULAR LYMPHOMA AT DIAGNOSIS USING PARAFFIN-EMBEDDED TISSUE SECTIONS

Selvi¹,

Kosova²,

Hekımgıl³

et al. 2012

Turk J Hematol

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Objective: Follicular lymphoma (FL) is one of the most common lymphomas, and is characterized by t(14;18)(q32;q21) in more than 80% of patients. The aim of this study was to determine the rate of t(14;18) positivity based onthe detection of mbr or mcr in paraffin-embedded tissue samples.Material and Methods: The study included 32 paraffin-embedded tissue samples collected from 32 consecutive FL patients that were diagnosed and followed-up at our hospital between 1999 and 2006. The MBR breakpoint wasidentified based on real-time PCR using a LightCycler v.2.0 t(14;18) Quantification Kit (MBR), multiplex PCR, and seminestedPCR. To identify the mcr breakpoint, real-time PCR was performed using specific primers and the FastStart DNAMaster SYBR Green I Kit. To detect t(14;18) via fluorescence in situ hybridization (FISH) nuclei from paraffin-embeddedtissue sections were extracted and used together with LSI IgH (immunoglobulin heavy chain) (spectrum green)/bcl-2(B-cell leukemia-lymphoma 2) (spectrum orange) probes.Results: The DNA and nuclei isolation success rate for B5 formalin-fixed, paraffin-embedded tissue sections (n = 12)was 42% and 33%, respectively, versus 95% and 60%, respectively, for 20 tissue sections fixed in formalin only. In all,24 paraffin-embedded tissue sections were analyzed and mbr positivity was observed in the DNA of 82.14% via seminested PCR, in 53.57% via multiplex PCR, and in 28.57% via real-time PCR. We did not detect mcr rearrangementin any of the samples. In all, 15 of 16 patients (93.75%) whose nuclei were successfully isolated were observed to bet(14;18) positive via the FISH method.Conclusion: Semi-nested PCR and FISH facilitated the genetic characterization of FL tumors. As such, FISH and PCR complement each other and are both essential for detecting t(14;18) translocation.

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Section: Discussionmentioning

confidence: 99%

MOLECULAR EVALUATION OF t(14;18)(bcl-2/IgH) TRANSLOCATION IN FOLLICULAR LYMPHOMA AT DIAGNOSIS USING PARAFFIN-EMBEDDED TISSUE SECTIONS

Selvi¹,

Kosova²,

Hekımgıl³

et al. 2012

Turk J Hematol

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“…The second element suggesting a FL hierarchy is the persistence of a t(14;18) + cell subset in lymph nodes from most FL patients in remission [34]. In line with the clinical course of FL, these remission-relapse episodes might thus reflect post-therapeutic replenishment of the malignant clone.…”

Section: Follicular Lymphomamentioning

confidence: 99%

Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

Gross

Quillet‐Mary

Ysebaert

et al. 2011

Cancers

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The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

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“…Currently, 'molecular remission' is an attainable goal with many therapeutic approaches. In the current issue of Leukemia and Lymphoma, Janikova et al [4] report on PCR monitoring that pushes the limit by sampling follow-up lymph node (LN) tissue, in addition to the peripheral blood (PB) and/or bone marrow (BM) sampling that is typically performed in follow-up studies.…”

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confidence: 98%

t(14;18) cells are getting hard to find

McLaughlin

2009

Leukemia & Lymphoma

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The persistence of t(14;18)-bearing cells in lymph nodes of patients with follicular lymphoma in complete remission: the evidence for ‘a lymphoma stem cell’

Cited by 8 publications

References 33 publications

MOLECULAR EVALUATION OF t(14;18)(bcl-2/IgH) TRANSLOCATION IN FOLLICULAR LYMPHOMA AT DIAGNOSIS USING PARAFFIN-EMBEDDED TISSUE SECTIONS

MOLECULAR EVALUATION OF t(14;18)(bcl-2/IgH) TRANSLOCATION IN FOLLICULAR LYMPHOMA AT DIAGNOSIS USING PARAFFIN-EMBEDDED TISSUE SECTIONS

Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

t(14;18) cells are getting hard to find

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