Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference

Baliakas, Panagiotis; Puiggros, Anna; Xochelli, Aliki; Sutton, Lesley-Ann; Nguyen‐Khac, Florence; Gardiner, Anne; Plevová, Karla; Minga, Eva; Hadzidimitriou, Anastasia; Walewska, Renata; McCarthy, Helen; Ortega, Margarita; Collado, Rosa; González, Teresa; Granada, Isabel; Luño, Elisa; Kotašková, Jana; Moysiadis, Theodoros; Davis, Zadie; Stavroyianni, Niki; Anagnostopoulos, Achilles; Strefford, Jonathan C.; Pospı́šilová, Šárka; Davi, Frédéric; Athanasiadou, Anastasia; Rosenquist, Richard; Oscier, David; Espinet, Blanca; Stamatopoulos, Kostas

doi:10.3324/haematol.2015.140202

Cited by 37 publications

(46 citation statements)

References 15 publications

(24 reference statements)

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“…Abbreviations: CA, chromosomal abnormalities; CB, chromosome banding; n, number; P, P value; UM, unmutated The second column represents for each variable the number of events and the total number of samples assessable for. 18,31,34,35 In addition to classical prognostic factors (age and Binet stage), certain cytogenetic and molecular features impacted the outcome of tri12 CLL patients in our cohort. The percent of tri12 corresponds to the percentage of interphase nuclei harboring trisomy 12 by FISH.…”

Section: Discussionmentioning

confidence: 90%

“…18,34,36 The two most recurrent trisomies associated with tri12 are tri18 and tri19. 18,34,36 The two most recurrent trisomies associated with tri12 are tri18 and tri19.…”

Section: Discussionmentioning

confidence: 99%

“…13,14 Other common CAs identified by means of conventional and molecular cytogenetic approaches include del (13)(q14), del (11)(q22-23), del (17) (p13), gain (2)(p), and del (6)(q21). 18 Indeed, accompanying chromosomal aberrations such as additional trisomies (tri18 and/or tri19), [18][19][20] 14q32 translocations (t [14;18](q32;q21) and t (14,19)(q32; q13)), [21][22][23][24][25] and 14q deletions 26,27 are commonly observed in tri12 CLL, and it has been suggested that patients harboring additional trisomies have better outcomes than patients with isolated tri12. [14][15][16][17] Tri12 was usually considered to be an intermediate-risk genetic lesion in newly diagnosed CLL and in the context of chemotherapy treatment, 14 although recent reports suggest that it confers more complex and heterogeneous clinical behavior.…”

Section: Introductionmentioning

confidence: 99%

“…These alterations influence survival. 18 Compared to CLL lacking this cytogenetic abnormality, tri12 CLL has a more atypical morphology and immunophenotype, 28,29 more frequent expression of the poor prognostic markers CD49d and CD38, more frequent NOTCH1 mutations, and unmutated (UM) IGHV gene status. 18 Indeed, accompanying chromosomal aberrations such as additional trisomies (tri18 and/or tri19), [18][19][20] 14q32 translocations (t [14;18](q32;q21) and t (14,19)(q32; q13)), [21][22][23][24][25] and 14q deletions 26,27 are commonly observed in tri12 CLL, and it has been suggested that patients harboring additional trisomies have better outcomes than patients with isolated tri12.…”

Section: Introductionmentioning

confidence: 99%

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Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A retrospective study from the French Innovative Leukemia Organization (FILO) working group

Roos‐Weil

Nguyen‐Khac

Chevret

et al. 2018

Genes Chromosomes & Cancer

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Trisomy 12 (tri12) is the second most frequent chromosomal aberration (15%-20%) in chronic lymphocytic leukemia (CLL). Tri12 confers an intermediate prognosis but is a heterogeneous entity. We examined whether additional mutational or chromosomal alterations might impact tri12 patient outcomes. This retrospective study, carried out by the French Innovative Leukemia Organization, included 188 tri12 patients with comprehensive information on immunoglobulin heavy chain (IGHV) gene status, karyotypic/FISH abnormalities, and NOTCH1, TP53, SF3B1, and MYD88 mutations. The main cytogenetic abnormalities associated with tri12 were del(13q) (25%), additional trisomies (14%) (including tri19 (10%) and tri18 (4%)), 14q32 translocations (10%), del(17p) (6.5%), del(14q) (4%), and del(11q) (4%). Unmutated (UM) IGHV, NOTCH1, and TP53, mutations were identified in respectively 66%, 25%, and 8.5% of cases. Multivariate analyses showed that additional trisomies (HR = 0.43, 95% CI = 0.23-0.78, P = .01) were associated with a significantly longer time to first treatment in Binet stage A patients and with a lower risk of relapse (HR = 0.37, 95% CI = 0.15-0.9, P = .03) in the overall tri12 population. Binet stage B/C, TP53 disruption, and UM IGHV status were associated with a shorter time to next treatment, while Binet stage B/C (HR = 4, 95% CI = 1.6-4.9, P = .002) and TP53 disruption (HR = 5, 95% CI = 1.94-12.66, P = .001) conferred shorter overall survival in multivariate comparisons. These data indicate that additional cytogenetic and mutational abnormalities, and particularly additional trisomies, IGHV status, and TP53 disruption, influence tri12 patient outcomes and could improve risk stratification in this population.

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Section: Discussionmentioning

confidence: 90%

“…18,34,36 The two most recurrent trisomies associated with tri12 are tri18 and tri19. 18,34,36 The two most recurrent trisomies associated with tri12 are tri18 and tri19.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A retrospective study from the French Innovative Leukemia Organization (FILO) working group

Roos‐Weil

Nguyen‐Khac

Chevret

et al. 2018

Genes Chromosomes & Cancer

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“…These phenotypic characteristics together with strong CD38 and weak CD200 expression corresponded to an atypical CLL or another CD51 B LPD, except for MCL as indicated by absence of t (11;14), cyclin D1 negativity and clinical behavior. According to Baliakas et al trisomy 12 can co-exist with trisomy 3 or trisomy 18 and 22 in CLL patients; such cases were reported to belong to CLL with mutated immunoglobulin heavy chain variable region genes and often express CD38 (which was also positive in our case) (30). Cytogenetic findings could not support or dismiss a specific entity.…”

Section: Discussionmentioning

confidence: 57%

CD5+ B lymphoproliferative disorder with subsequent development of plasma cell leukaemia: Diagnostic and aetiologic reasoning

Gounari

Kaiafa

Κoletsa

et al. 2017

Cytometry Part B Clinical

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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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Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference

Cited by 37 publications

References 15 publications

Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A retrospective study from the French Innovative Leukemia Organization (FILO) working group

Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A retrospective study from the French Innovative Leukemia Organization (FILO) working group

CD5+ B lymphoproliferative disorder with subsequent development of plasma cell leukaemia: Diagnostic and aetiologic reasoning

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

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