Two Distinct &lt;b&gt;&lt;i&gt;BCL2&lt;/i&gt;&lt;/b&gt; Rearrangements, Each Observed in 2 Independent Subclones, Evolving from a Founder Clone with Trisomy 12 in a Unique Case of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Peterson, Jess F.; Shah, Rajul; Kobrinski, Daniel

doi:10.1159/000474926

Cited by 4 publications

(6 citation statements)

References 11 publications

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“…This is supported by numerous studies reporting on multiple neoplastic "subclones" coexisting within the CLL population, which have arisen from clonal populations harboring different genetic aberrations or acquisition of additional abnormalities over time (16,(46)(47)(48)(49). Small subclones independently emerging in CLL +12 may include BCL2 translocations [e.g., t(14;18)(q32;q21) or t(2;18)(p11.2;q21)] and deletions of TP53/del(17p), usually consisting of 0.5-7.5% of cells (10,(48)(49)(50). These subclones are associated with disease progression or relapse and can therefore present as independent risk and prognostic factors (10,11,14,46,(48)(49)(50).…”

Section: Immuno-flowfish For Detection Of Subclones In Cllmentioning

confidence: 99%

“…Small subclones independently emerging in CLL +12 may include BCL2 translocations [e.g., t(14;18)(q32;q21) or t(2;18)(p11.2;q21)] and deletions of TP53/del(17p), usually consisting of 0.5-7.5% of cells (10,(48)(49)(50). These subclones are associated with disease progression or relapse and can therefore present as independent risk and prognostic factors (10,11,14,46,(48)(49)(50). Specifically, patients with >60% of cells with +12 had a worse outcome in terms of overall and disease-free survival.…”

Section: Immuno-flowfish For Detection Of Subclones In Cllmentioning

confidence: 99%

“…Prognosis in CLL can vary significantly depending on the genetic aberration which can have profound effects on overall survival and response to treatment (7). Trisomy 12, or the gain of one chromosome 12 (+12), is a cytogenetic aberration unique to CLL and is usually found in 10-20% of cases (8)(9)(10)(11)(12)(13)(14). Trisomy 12 cases are associated with an intermediate prognostic outlook and presence of this aberration does not alter disease management beyond the standard of care (11)(12)(13)(14)(15).…”

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confidence: 99%

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“Immuno‐flowFISH” for the Assessment of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia

et al. 2019

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Imaging flow cytometry is emerging as a diagnostic tool for the assessment of leukemia. It has the functionality of standard flow cytometry and generates high‐resolution digital images of each cell with quantifiable numerical data. We demonstrate the use of an automated high‐throughput method for performing fluorescence in situ hybridization (FISH) on immunophenotyped whole cells in suspension and analyzed by imaging flow cytometry, a technique called “Immuno‐flowFISH”. The aim of this study was to demonstrate the application of immuno‐flowFISH for the detection of chromosomal abnormalities in CLL, specifically trisomy 12 and del(17p). Mononuclear cells were isolated and immunophenotyped with fluorescently conjugated CD3, CD5, and CD19 monoclonal antibodies. Following fixation, cells were permeabilized, dsDNA denatured and hybridized with chromosome 12 or 17 enumeration (CEP 12 and CEP17) and 17p12 locus‐specific FISH probes. Cells were analyzed on the Amnis ImageStream®X Mark II to assess the number and percent FISH‐positive CLL cells and the ratio of FISH spot counts for CD5/CD19‐positive CLL cells to CD3/CD5‐positive T cells (FISH “mean spot ratio”). Deletion of 17p was detected in about 8% of cases to date, with del(17p) ranged from 3.5–22.8% and the FISH “mean spot ratio” 0.86–0.96. Immuno‐flowFISH also detected a minimal residual disease case with +12 with a limit of detection of 0.13% and a rare case that presented with atypical phenotype and cytogenetics. Immuno‐flowFISH could detect del(17p) in phenotypically identified CD5/CD19‐positive B‐cells. The 100‐fold increase in analyzed cells, as well as the addition of cell phenotype increased the sensitivity and specificity over current clinical FISH testing. Furthermore, immuno‐flowFISH analysis demonstrated specific utility in unique clinical scenarios such as residual disease and atypical biology cases which may be of significant benefit with regards to prognostication and MRD analysis. The method will assist in therapeutic decision making and disease monitoring for many hematological malignancies. © 2019 International Society for Advancement of Cytometry

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Section: Immuno-flowfish For Detection Of Subclones In Cllmentioning

confidence: 99%

Section: Immuno-flowfish For Detection Of Subclones In Cllmentioning

confidence: 99%

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confidence: 99%

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“Immuno‐flowFISH” for the Assessment of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia

et al. 2019

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“…In a recent issue of Acta Haematologica , Peterson et al [4 ]report the case of a CLL patient with clonal evolution after 8 years of follow-up, from a trisomy 12 and t(14;18)(q32;q21) deletion ( IGH-BCL2 ) observed at the time of diagnosis. During evolution, conventional cytogenetics in peripheral blood revealed 2 different clones associated with trisomy 12.…”

mentioning

confidence: 99%

“…However, conventional cytogenetics, along with stimulating techniques, can be recommended for the diagnosis and follow-up of patients with CLL, to discard complex karyotype or to illustrate cases like the one described by Peterson et al [4]. …”

mentioning

confidence: 99%

Genetic Heterogeneity in Chronic Lymphocytic Leukemia: What Can Conventional Cytogenetics Add?

Hernández‐Rivas

Marín²

2017

Acta Haematol

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Relapse of follicular lymphoma arising from a non‐t(14;18) clone

Otsuka

Nishikori

Fujimoto

et al. 2020

eJHaem

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Intraclonal diversity is commonly observed in patients with follicular lymphoma (FL), whereas tumor cells at the onset and relapse usually share early genetic events such as VDJ rearrangement of the immunoglobulin genes and t(14;18) translocation. We report a case of FL with relapse with FL that was clonally different from the tumor cells at onset. A 59‐year‐old male presented with paraaortic lymph node swelling and thickening of the right renal pelvic and ureteral wall was histologically diagnosed as FL, grade 1. Karyotypic analysis revealed t(14;18)(q32;q21) with +12 and +der(18)t(14;18). Ten years after the initial diagnosis, he suddenly developed systemic lymphadenopathy as a second relapse, and histological examination led to the diagnosis of FL grade 3B with diffuse large B‐cell lymphoma. Surprisingly, karyotypic analysis demonstrated the presence of +12 and 3q27 abnormality, which was proved to be a BCL6 translocation by fluorescence in situ hybridization, but the absence of t(14;18)(q32;q21). We compared VDJ rearrangement of the FL cells at onset and relapse and found that they were completely independent of each other. These tumor cells sharetrisomy 12 as a common genetic abnormality, and it is speculated that trisomy 12 may have occurred earlier than BCL2 and BCL6 translocations. These results suggest that there can even be cases of “relapse” of FL with an independent origin of the primary tumor cells. Our observation highlights the importance of re‐biopsy of relapsed FL, especially when it occurs after a long remission with different clinical presentation from that at the onset.

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Two Distinct <b><i>BCL2</i></b> Rearrangements, Each Observed in 2 Independent Subclones, Evolving from a Founder Clone with Trisomy 12 in a Unique Case of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Cited by 4 publications

References 11 publications

“Immuno‐flowFISH” for the Assessment of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia

“Immuno‐flowFISH” for the Assessment of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia

Genetic Heterogeneity in Chronic Lymphocytic Leukemia: What Can Conventional Cytogenetics Add?

Relapse of follicular lymphoma arising from a non‐t(14;18) clone

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