Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #2

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Prognostic impact of epigenetic classification in chronic lymphocytic leukemia : The case of subset #2. / Bhoi, Sujata; Ljungström, Viktor; Baliakas, Panagiotis; Mattsson, Mattias; Smedby, Karin E.; Juliusson, Gunnar; Rosenquist, Richard; Mansouri, Larry.

In: Epigenetics, Vol. 11, No. 6, 02.06.2016, p. 449-455.

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Bhoi, S, Ljungström, V, Baliakas, P, Mattsson, M, Smedby, KE, Juliusson, G, Rosenquist, R & Mansouri, L 2016, 'Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #2', Epigenetics, vol. 11, no. 6, pp. 449-455. https://doi.org/10.1080/15592294.2016.1178432

APA

Bhoi, S., Ljungström, V., Baliakas, P., Mattsson, M., Smedby, K. E., Juliusson, G., ... Mansouri, L. (2016). Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #2. Epigenetics, 11(6), 449-455. https://doi.org/10.1080/15592294.2016.1178432

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Bhoi, Sujata ; Ljungström, Viktor ; Baliakas, Panagiotis ; Mattsson, Mattias ; Smedby, Karin E. ; Juliusson, Gunnar ; Rosenquist, Richard ; Mansouri, Larry. / Prognostic impact of epigenetic classification in chronic lymphocytic leukemia : The case of subset #2. In: Epigenetics. 2016 ; Vol. 11, No. 6. pp. 449-455.

RIS

TY - JOUR

T1 - Prognostic impact of epigenetic classification in chronic lymphocytic leukemia

T2 - Epigenetics

AU - Bhoi, Sujata

AU - Ljungström, Viktor

AU - Baliakas, Panagiotis

AU - Mattsson, Mattias

AU - Smedby, Karin E.

AU - Juliusson, Gunnar

AU - Rosenquist, Richard

AU - Mansouri, Larry

PY - 2016/6/2

Y1 - 2016/6/2

N2 - ABSTRACT: Based on the methylation status of 5 single CpG sites, a novel epigenetic classification of chronic lymphocytic leukemia (CLL) was recently proposed, classifying CLL patients into 3 clinico-biological subgroups with different outcome, termed memory like CLL (m-CLL), naïve like CLL (n-CLL), and a third intermediate CLL subgroup (i-CLL). While m-CLL and n-CLL patients at large corresponded to patients carrying mutated and unmutated IGHV genes, respectively, limited information exists regarding the less defined i-CLL group. Using pyrosequencing, we investigated the prognostic impact of the proposed 5 CpG signature in a well-characterized CLL cohort (135 cases), including IGHV-mutated and unmutated patients as well as clinically aggressive stereotyped subset #2 patients. Overall, we confirmed the signature's association with established prognostic markers. Moreover, in the presence of the IGHV mutational status, the epigenetic signature remained independently associated with both time-to-first-treatment and overall survival in multivariate analyses. As a prime finding, we observed that subset #2 patients were predominantly classified as i-CLL, probably reflecting their borderline IGHV mutational status (97–99% germline identity), though having a similarly poor prognosis as n-CLL patients. In summary, we validated the epigenetic classifier as an independent factor in CLL prognostication and provide further evidence that subset #2 is a member of the i-CLL group, hence supporting the existence of a third, intermediate epigenetic subgroup.

AB - ABSTRACT: Based on the methylation status of 5 single CpG sites, a novel epigenetic classification of chronic lymphocytic leukemia (CLL) was recently proposed, classifying CLL patients into 3 clinico-biological subgroups with different outcome, termed memory like CLL (m-CLL), naïve like CLL (n-CLL), and a third intermediate CLL subgroup (i-CLL). While m-CLL and n-CLL patients at large corresponded to patients carrying mutated and unmutated IGHV genes, respectively, limited information exists regarding the less defined i-CLL group. Using pyrosequencing, we investigated the prognostic impact of the proposed 5 CpG signature in a well-characterized CLL cohort (135 cases), including IGHV-mutated and unmutated patients as well as clinically aggressive stereotyped subset #2 patients. Overall, we confirmed the signature's association with established prognostic markers. Moreover, in the presence of the IGHV mutational status, the epigenetic signature remained independently associated with both time-to-first-treatment and overall survival in multivariate analyses. As a prime finding, we observed that subset #2 patients were predominantly classified as i-CLL, probably reflecting their borderline IGHV mutational status (97–99% germline identity), though having a similarly poor prognosis as n-CLL patients. In summary, we validated the epigenetic classifier as an independent factor in CLL prognostication and provide further evidence that subset #2 is a member of the i-CLL group, hence supporting the existence of a third, intermediate epigenetic subgroup.

KW - CLL

KW - epigenetic classification

KW - methylation

KW - prognosis

UR - http://www.scopus.com/inward/record.url?scp=84973167177&partnerID=8YFLogxK

U2 - 10.1080/15592294.2016.1178432

DO - 10.1080/15592294.2016.1178432

M3 - Article

VL - 11

SP - 449

EP - 455

JO - Epigenetics

JF - Epigenetics

SN - 1559-2294

IS - 6

ER -