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Baliakas, PanagiotisORCID iD iconorcid.org/0000-0002-5634-7156
Alternative names
Publications (10 of 54) Show all publications
Baliakas, P., Jeromin, S., Iskas, M., Puiggros, A., Plevova, K., Nguyen-Khac, F., . . . Stamatopoulos, K. (2019). Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood, 133(11), 1205-1216
Open this publication in new window or tab >>Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact
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2019 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 133, no 11, p. 1205-1216Article in journal (Refereed) Published
Abstract [en]

Recent evidence suggests that complex karyotype (CK) defined by the presence of >= 3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with >= 5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and 112,119 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hyper-mutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with 112,119, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with >= 5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-381085 (URN)10.1182/blood-2018-09-873083 (DOI)000461508300007 ()30602617 (PubMedID)
Funder
EU, Horizon 2020EU, Horizon 2020Swedish Research Council
Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved
Moysiadis, T., Baliakas, P., Rossi, D., Catherwood, M., Strefford, J. C., Delgado, J., . . . Stamatopoulos, K. (2019). Different time-dependent changes of risk for evolution in chronic lymphocytic leukemia with mutated or unmutated antigen B cell receptors [Letter to the editor]. Leukemia, 33(7), 1801-1805
Open this publication in new window or tab >>Different time-dependent changes of risk for evolution in chronic lymphocytic leukemia with mutated or unmutated antigen B cell receptors
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2019 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 33, no 7, p. 1801-1805Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-390327 (URN)10.1038/s41375-018-0322-7 (DOI)000473724900022 ()30679797 (PubMedID)
Funder
EU, Horizon 2020, 702714EU, Horizon 2020EU, Horizon 2020Swedish Research CouncilKnut and Alice Wallenberg FoundationSwedish Cancer SocietyErik, Karin och Gösta Selanders Foundation
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Baliakas, P., Moysiadis, T., Hadzidimitriou, A., Xochelli, A., Jeromin, S., Agathangelidis, A., . . . Stamatopoulos, K. (2019). Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia. Haematologica, 104(2), 360-369
Open this publication in new window or tab >>Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia
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2019 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, no 2, p. 360-369Article in journal (Refereed) Published
Abstract [en]

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to first -treatment and a treatment probability at Five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or ST3B1 mutations were associated with the shortest time-to-First treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.

Place, publisher, year, edition, pages
FERRATA STORTI FOUNDATION, 2019
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-377215 (URN)10.3324/haematol.2018.195032 (DOI)000457460800032 ()30262567 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
Baliakas, P., Mattsson, M., Hadzidimitriou, A., Minga, E., Agathangelidis, A., Sutton, L. A., . . . Stamatopoulos, K. (2018). No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy [Letter to the editor]. Haematologica, 103(4), E158-E161
Open this publication in new window or tab >>No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy
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2018 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 4, p. E158-E161Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
FERRATA STORTI FOUNDATION, 2018
National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-356894 (URN)10.3324/haematol.2017.182634 (DOI)000428242100006 ()29269523 (PubMedID)
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09Bibliographically approved
Norberg, A., Rosen, A., Raaschou-Jensen, K., Kjeldsen, L., Moilanen, J. S., Paulsson-Karlsson, Y., . . . Hultdin, M. (2018). Novel variants in Nordic patients referred for genetic testing of telomere-related disorders. European Journal of Human Genetics, 26(6), 858-867
Open this publication in new window or tab >>Novel variants in Nordic patients referred for genetic testing of telomere-related disorders
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2018 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 26, no 6, p. 858-867Article in journal (Refereed) Published
Abstract [en]

Telomere-related disorders are a clinically and genetically heterogeneous group of disorders characterized by premature telomere shortening and proliferative failure of a variety of tissues. This study reports the spectrum of telomere-related gene variants and telomere length in Nordic patients referred for genetic testing due to suspected telomere-related disorder. We performed Sanger sequencing of the genes TERT, TERC, DKC1, and TINF2 on 135 unrelated index patients and measured telomere length by qPCR on DNA from peripheral blood leukocytes. We identified pathogenic or likely pathogenic variants in 10 index patients, all of which had short telomeres compared to age-matched healthy controls. Six of the 10 variants were novel; three in TERC (n.69_74dupAGGCGC, n.122_125delGCGG, and n.407_408delinsAA) and three in TERT (p.(D684G), p.(R774*), and p.(*1133Wext*39)). The high proportion of novel variants identified in our study highlights the need for solid interpretation of new variants that may be detected. Measurement of telomere length is a useful approach for evaluating pathogenicity of genetic variants associated with telomere-related disorders.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-357385 (URN)10.1038/s41431-018-0112-8 (DOI)000433424200010 ()29483670 (PubMedID)
Funder
Swedish Childhood Cancer FoundationThe Kempe Foundations
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-08-23Bibliographically approved
Baliakas, P., Kättström, M., Rossing, M. & Amini, R.-M. (2018). Refractory chronic "ITP": When platelet size matters. Clinical Case Reports, 6(9), 1779-1780
Open this publication in new window or tab >>Refractory chronic "ITP": When platelet size matters
2018 (English)In: Clinical Case Reports, E-ISSN 2050-0904, Vol. 6, no 9, p. 1779-1780Article in journal (Refereed) Published
Abstract [en]

Key Clinical Message Inherited conditions associated with thrombocytopenia should be included in the differential diagnosis of young patients with refractory immune thrombocytopenia (ITP), even in the absence of a positive family history. Early identification of such conditions is of vital importance in order to reach the right diagnosis and avoid unnecessary or even harmful medication.

Keywords
ear nose and throat, genetics, hematology, nephrology, pediatrics and adolescent medicine
National Category
Hematology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-365664 (URN)10.1002/ccr3.1711 (DOI)000444225900027 ()30214762 (PubMedID)
Available from: 2018-11-15 Created: 2018-11-15 Last updated: 2019-03-29Bibliographically approved
Xochelli, A., Baliakas, P., Kavakiotis, I., Agathangelidis, A., Sutton, L. A., Minga, E., . . . Stamatopoulos, K. (2017). Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes. Clinical Cancer Research, 23(17), 5292-5301
Open this publication in new window or tab >>Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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2017 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 17, p. 5292-5301Article in journal (Refereed) Published
Abstract [en]

Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management.  

Keywords
B-cell receptors, gene mutational status, antigen receptors, CD38 expression, genomic aberrations, sequence-analysis, I-antigen, immunoglobulin, antibodies, dna
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-334402 (URN)10.1158/1078-0432.CCR-16-3100 (DOI)000409037300034 ()28536306 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2017-12-08 Created: 2017-12-08 Last updated: 2017-12-11Bibliographically approved
Baliakas, P., Jeronim, S., Iskas, M., Puiggros, A., Plevova, K., Xochelli, A., . . . Haferlach, C. (2017). Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations with other bio-markers and clinical impact. Paper presented at XVII International Workshop on Chronic Lymphocytic Leukemia 2017 May 12-15, 2017, New York. Leukemia and Lymphoma, 58(Supplement: 1), 65-66
Open this publication in new window or tab >>Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations with other bio-markers and clinical impact
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2017 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 58, no Supplement: 1, p. 65-66Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-350210 (URN)10.1080/10428194.2017.1377942 (DOI)000423431100054 ()
Conference
XVII International Workshop on Chronic Lymphocytic Leukemia 2017 May 12-15, 2017, New York
Note

Meeting Abstract: 72

Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-05-08Bibliographically approved
Baliakas, P., Jeromin, S., Iskas, M., Puiggros, A., Plevova, K., Xochelli, A., . . . Haferlach, C. (2017). CYTOGENETIC COMPLEXITY IN CHRONIC LYMPHOCYTIC LEUKEMIA: DEFINITIONS, ASSOCIATIONS WITH OTHER BIOMARKERS AND CLINICAL IMPACT; A RETROSPECTIVE STUDY ON BEHALF OF ERIC. Paper presented at 22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN. Haematologica, 102(Suppl. 2), 170-170, Article ID S461.
Open this publication in new window or tab >>CYTOGENETIC COMPLEXITY IN CHRONIC LYMPHOCYTIC LEUKEMIA: DEFINITIONS, ASSOCIATIONS WITH OTHER BIOMARKERS AND CLINICAL IMPACT; A RETROSPECTIVE STUDY ON BEHALF OF ERIC
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2017 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no Suppl. 2, p. 170-170, article id S461Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
FERRATA STORTI FOUNDATION, 2017
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-377414 (URN)000404127001355 ()
Conference
22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN
Available from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-02-20Bibliographically approved
Young, E., Noerenberg, D., Mansouri, L., Ljungström, V., Frick, M., Sutton, L. A., . . . Damm, F. (2017). EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia. Leukemia, 31(7), 1547-1554
Open this publication in new window or tab >>EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
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2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 7, p. 1547-1554Article in journal (Refereed) Published
Abstract [en]

Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n = 1283) and two validation cohorts (UK CLL4 trial patients, n = 366; CLL Research Consortium (CRC) patients, n = 490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2- mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.

National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-314928 (URN)10.1038/leu.2016.359 (DOI)000404745300009 ()27890934 (PubMedID)
Note

E.Y. and D.N. contributed equally to this study as joint first authors.

R.R. and F.D. contributed equally as joint senior authors.

Available from: 2017-02-07 Created: 2017-02-07 Last updated: 2017-09-28Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5634-7156

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