Oncogenetic landscape of T-cell lymphoblastic lymphomas compared to T-cell acute lymphoblastic leukemia.
Adolescent
Carcinogenesis
/ pathology
Cell Transformation, Neoplastic
/ pathology
Class I Phosphatidylinositol 3-Kinases
Humans
Leukemia-Lymphoma, Adult T-Cell
/ pathology
Lymphoma, T-Cell
Phosphatidylinositol 3-Kinases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
/ genetics
T-Lymphocytes
/ pathology
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
16
02
2022
accepted:
08
04
2022
revised:
08
04
2022
pubmed:
14
5
2022
medline:
1
9
2022
entrez:
13
5
2022
Statut:
ppublish
Résumé
In the latest 2016 World Health Organization classification of hematological malignancies, T-cell lymphoblastic lymphoma (T-LBL) and lymphoblastic leukemia (T-ALL) are grouped together into one entity called T-cell lymphoblastic leukemia/lymphoma (T-LBLL). However, the question of whether these entities represent one or two diseases remains. Multiple studies on driver alterations in T-ALL have led to a better understanding of the disease while, so far, little data on genetic profiles in T-LBL is available. We sought to define recurrent genetic alterations in T-LBL and provide a comprehensive comparison with T-ALL. Targeted whole-exome next-generation sequencing of 105 genes, multiplex ligation-dependent probe amplification, and quantitative PCR allowed comprehensive genotype assessment in 818, consecutive, unselected, newly diagnosed patients (342 T-LBL vs. 476 T-ALL). The median age at diagnosis was similar in T-LBL and T-ALL (17 vs. 15 years old, respectively; p = 0.2). Although we found commonly altered signaling pathways and co-occurring mutations, we identified recurrent dissimilarities in actionable gene alterations in T-LBL as compared to T-ALL. HOX abnormalities (TLX1 and TLX3 overexpression) were more frequent in T-ALL (5% of T-LBL vs 13% of T-ALL had TLX1 overexpression; p = 0.04 and 6% of T-LBL vs 17% of T-ALL had TLX3 overexpression; p = 0.006). The PI3K signaling pathway was significantly more frequently altered in T-LBL as compared to T-ALL (33% vs 19%; p < 0.001), especially through PIK3CA alterations (9% vs 2%; p < 0.001) with PIK3CA
Identifiants
pubmed: 35562412
doi: 10.1038/s41379-022-01085-9
pii: S0893-3952(22)00278-2
doi:
Substances chimiques
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1227-1235Informations de copyright
© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Références
Arber, D. A., Orazi, A., Hasserjian, R., Thiele, J., Borowitz, M. J., le Beau, M. M. et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127, 2391–2405 (2016).
Kroeze, E., Loeffen, J. L. C., Poort, V. M. & Meijerink, J. P. P. T-cell lymphoblastic lymphoma and leukemia: different diseases from a common premalignant progenitor? Blood Adv 4, 3466–3473 (2020).
van der Zwet, J. C. G., Cordo’, V., Canté-Barrett, K. & Meijerink, J. P. P. Multi-omic approaches to improve outcome for T-cell acute lymphoblastic leukemia patients. Adv Biol Regul 74, 100647 (2019).
Burkhardt, B., Zimmermann, M., Oschlies, I., Niggli, F., Mann, G., Parwaresch, R. et al. The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. Br J Haematol 131, 39–49 (2005).
Burkhardt, B., Reiter, A., Landmann, E., Lang, P., Lassay, L., Dickerhoff, R. et al. Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the Berlin-Frankfurt-Muenster group. J Clin Oncol 27, 3363–3369 (2009).
Hagedorn, N., Acquaviva, C., Fronkova, E., Von Stackelberg, A., Barth, A., Zur Stadt, U. et al. Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of “isolated” and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group. Blood 110, 4022–4029 (2007).
Basso, K., Mussolin, L., Lettieri, A., Brahmachary, M., Lim, W. K., Califano, A. et al. T-cell lymphoblastic lymphoma shows differences and similarities with T-cell acute lymphoblastic leukemia by genomic and gene expression analyses. Genes Chromosomes Cancer 50, 1063–1075 (2011).
Bonn, B. R., Huge, A., Rohde, M., Oschlies, I., Klapper, W., Voss, R. et al. Whole exome sequencing hints at a unique mutational profile of paediatric T-cell lymphoblastic lymphoma. Br J Haematol vol. 168 308–313 (2015).
Feng, H., Stachura, D. L., White, R. M., Gutierrez, A., Zhang, L., Sanda, T. et al. T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell 18, 353–366 (2010).
Patel, J. L., Smith, L. M., Anderson, J., Abromowitch, M., Campana, D., Jacobsen, J. et al. The immunophenotype of T-lymphoblastic lymphoma in children and adolescents: A children’s oncology group report. Br J Haematol 159, 454–461 (2012).
Bernard, A., Boumsell, L., Reinherz, E., Nadler, L., Ritz, J., Coppin, H. et al. Cell surface characterization of malignant T cells from lymphoblastic lymphoma using monoclonal antibodies: evidence for phenotypic differences between malignant T cells from patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. Blood 57, 1105–1110 (1981).
Uyttebroeck, A., Vanhentenrijk, V., Hagemeijer, A., Boeckx, N., Renard, M., Wlodarska, I. et al. Is there a difference in childhood T-cell acute lymphoblastic leukaemia and T-cell lymphoblastic lymphoma? Leuk Lymphoma 48, 1745–1754 (2007).
Haider, Z., Landfors, M., Golovleva, I., Erlanson, M., Schmiegelow, K., Flægstad, T. et al. DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma. Blood Cancer J 10, 45 (2020).
Terwilliger, T. & Abdul-Hay, M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 7, e577 (2017).
Pillon, M., Piglione, M., Garaventa, A., Conter, V., Giuliano, M., Arcamone, G. et al. Long-term results of AIEOP LNH-92 protocol for the treatment of pediatric lymphoblastic lymphoma: a report of the Italian association of pediatric hematology and oncology. Pediatr Blood Cancer 53, 953–959 (2009).
Goldberg, J. M., Silverman, L. B., Levy, D. E., Dalton, V. K., Gelber, R. D., Lehmann, L. et al. Childhood T-cell acute lymphoblastic leukemia: The Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium experience. J Clin Oncol vol. 21 3616–3622 (2003).
Sandlund, J. T., Pui, C. H., Zhou, Y., Behm, F. G., Onciu, M., Razzouk, B. I. et al. Effective treatment of advanced-stage childhood lymphoblastic lymphoma without prophylactic cranial irradiation: Results of St Jude NHL13 study. Leukemia 23, 1127–1130 (2009).
Huguet, F., Chevret, S., Leguay, T., Thomas, X., Boissel, N., Escoffre-Barbe, M. et al. Intensified therapy of acute lymphoblastic leukemia in adults: Report of the randomized GRAALL-2005 clinical trial. J Clin Oncol 36, 2514–2523 (2018).
Oudot, C., Auclerc, M. F., Levy, V., Porcher, R., Piguet, C., Perel, Y. et al. Prognostic factors for leukemic induction failure in children with acute lymphoblastic leukemia and outcome after salvage therapy: The FRALLE 93 study. J Clin Oncol 26, 1496–1503 (2008).
Burkhardt, B., Taj, M., Garnier, N., Minard-Colin, V., Hazar, V., Mellgren, K. et al. Treatment and outcome analysis of 639 relapsed non-hodgkin lymphomas in children and adolescents and resulting treatment recommendations. Cancers 13, 2075 (2021).
Trinquand, A., Tanguy-Schmidt, A., Abdelali, R. Ben, Lambert, J., Beldjord, K., Lengliné, E. et al. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-Cell acute lymphoblastic leukemia: a group for research in adult acute lymphoblastic leukemia study. J Clin Oncol 31, 4333–4342 (2013).
Bond, J., Marchand, T., Touzart, A., Cieslak, A., Trinquand, A., Sutton, L. et al. An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: A group for research in adult acute lymphoblastic leukemia study. Haematologica 101, 732–740 (2016).
Alcazer, V. StatAid: An R package with a graphical user interface for data analysis. J. Open Source Softw 5, 2630 (2020).
Dadi, S., Le Noir, S., Payet-Bornet, D., Lhermitte, L., Zacarias-Cabeza, J., Bergeron, J. et al. TLX Homeodomain Oncogenes Mediate T Cell Maturation Arrest in T-ALL via Interaction with ETS1 and Suppression of TCRα Gene Expression. Cancer Cell 21, 563–576 (2012).
Cavé, H., Suciu, S., Preudhomme, C., Poppe, B., Robert, A., Uyttebroeck, A. et al. Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: Results of EORTC studies 58881 and 58951. Blood 103, 442–450 (2004).
Ballerini, P., Landman-Parker, J., Cayuela, J. M., Asnafi, V., Labopin, M., Gandemer, V. et al. Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome. Haematologica 93, 1658–1665 (2008).
Balbach, S. T., Makarova, O., Bonn, B. R., Zimmermann, M., Oschlies, I., Klapper, W. et al. Proposal of a genetic classifier for risk group stratification in pediatric T-cell lymphoblastic lymphoma reveals differences from adult T-cell lymphoblastic leukemia. Leukemia vol. 30 970–973 (2016).
Khanam, T., Sandmann, S., Seggewiss, J., Ruether, C., Zimmermann, M., Norvil, A. B. et al. I Integrative genomic analysis of pediatric T-cell lymphoblastic lymphoma reveals candidates of clinical significance. Blood 137, 2347–2359 (2021).
Gutierrez, A., Sanda, T., Grebliunaite, R., Carracedo, A., Salmena, L., Ahn, Y. et al. High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia. Blood 114, 647–650 (2009).
Zuurbier, L., Petricoin, E. F., Vuerhard, M. J., Calvert, V., Kooi, C., Buijs- Gladdines, J. G. C. A. M. et al. The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia. Haematologica 97, 1405–1413 (2012).
Li, Z., Song, Y., Zhang, Y., Li, C., Wang, Y., Xue, W. et al. Genomic and outcome analysis of adult T-cell lymphoblastic lymphoma. Haematologica vol. 105 E107–E110 (2020).
Fayard, E., Moncayo, G., Hemmings, B. A. & Holländer, G. A. Phosphatidylinositol 3-kinase signaling in thymocytes: The need for stringent control. Sci Signal. 3, 1–13 (2010).
Chen, Y., Hou, Q., Yan, W., J, L., D, C., Z, L. et al. PIK3CA is critical for the proliferation, invasiveness, and drug resistance of human tongue carcinoma cells. Oncol Res. 19, 563–571 (2011).
Matsuoka, T., Yashiro, M., Nishioka, N., Hirakawa, K., Olden, K. & Roberts, J. D. PI3K/Akt signalling is required for the attachment and spreading, and growth in vivo of metastatic scirrhous gastric carcinoma. Br J Cancer 106, 1535–1542 (2012).
Li, B., Xu, W., Lam, A., Y, W., HF, H., XY, G. et al. S Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy. Oncotarget 8, 38755–38766 (2017).
Hirsch, E., Ciraolo, E., Franco, I., Ghigo, A. & Martini, M. PI3K in cancer–stroma interactions: bad in seed and ugly in soil. Oncogene 2014 33:24 33, 3083–3090 (2013).
Venot, Q., Blanc, T., Rabia, S. H., Berteloot, L., Ladraa, S. & Duong, J. et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature 558, 540–546 (2021).
André, F., Ciruelos, E., Rubovszky, G., Campone, M., Loibl, S., Rugo, H. S. et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer. N Engl J Med. 380, 1929–1940 (2019).
Weng, A. P., Ferrando, A. A., Lee, W., Morris IV, J. P., Silverman, L. B., Sanchez- Irizarry, C. et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306, 269–271 (2004).
Aref, S., el Agdar, M., Salama, O., Zeid, T. A. & Sabry, M. Significance of NOTCH1 mutations detections in T-acute lymphoblastic leukemia patients. Cancer Biomark 27, 157–162 (2020).
Clappier, E., Collette, S., Grardel, N., Girard, S., Suarez, L., Brunie, G. et al. NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951. Leukemia 24, 2023–2031 (2010).
Breit, S., Stanulla, M., Flohr, T., Schrappe, M., Ludwig, W. D., Tolle, G. et al. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood 108, 1151–1157 (2006).
Bonn, B. R., Rohde, M., Zimmermann, M., Krieger, D., Oschlies, I., Niggli, F. et al. Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence. Blood 121, 3153–3160 (2013).
Lepretre, S., Touzart, A., Vermeulin, T., Picquenot, J. M., Tanguy-Schmidt, A., Salles, G. et al. Pediatric-like acute lymphoblastic leukemia therapy in adults with lymphoblastic lymphoma: the GRAALL-LYSA LL03 study. J Clin Oncol. 34, 572–580 (2016).
Schäfer, V., Ernst, J., Rinke, J., Winkelmann, N., Beck, J. F., Hochhaus, A. et al. EZH2 mutations and promoter hypermethylation in childhood acute lymphoblastic leukemia. J Cancer Res Clin Oncol 142, 1641–1650 (2016).
Ntziachristos, P., Tsirigos, A., Vlierberghe, P. Van, Nedjic, J., Trimarchi, T.,Flaherty, M. S. et al. Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. Nat Med 18, 296–301 (2012).
Andrieu, G. P., Kohn, M., Simonin, M., Smith, C., Cieslak, A., Dourthe, M.-E. et al. PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL. Blood 138, 1855–1869 (2021).
Broux, M., Prieto, C., Demeyer, S., Bempt, M. vanden, Alberti-Servera, L., Lodewijckx, I. et al. Suz12 inactivation cooperates with JAK3 mutant signaling in the development of T-cell acute lymphoblastic leukemia. Blood 134, 1323-1336 (2019).
Yuan, S., Wang, X., Hou, S., Guo, T., Lan, Y., Yang, S. et al. PHF6 and JAK3 mutations cooperate to drive T-cell acute lymphoblastic leukemia progression. Leukemia 36, 370–382 (2022).
Kurzer, J. H. & Weinberg, O. K. PHF6 mutations in hematologic malignancies. Front Oncol 11, 704471 (2021).
Liu, Y., Easton, J., Shao, Y., Maciaszek, J., Wang, Z., Wilkinson, M. R. et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet 49, 1211–1218 (2017).
Zhang, H., Wang, H., Qian, X., Gao, S., Xia, J., Liu, J. et al Genetic mutational analysis of pediatric acute lymphoblastic leukemia from a single center in China using exon sequencing. BMC Cancer 20, 211 (2020).
Stengel, A., Kern, W., Haferlach, T., Schnittger, S., Zenger, M. & Haferlach, C. Comparison of TP53 Alterations in Hematological Malignancies. Blood 126, 4819–4819 (2015).
Cluzeau, T., Sebert, M., Rahmé, R., Cuzzubbo, S., Lehmann-Che, J., Madelaine, I. et al. Eprenetapopt Plus Azacitidine In TP53-mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase Ii Study by the Groupe Francophone des Myélodysplasies (GFM). J Clin Oncol 39, 1575–1583 (2021).
Sallman, D. A., DeZern, A. E., Garcia-Manero, G., Steensma, D. P., Roboz, G. J., Sekeres, M. A. et al. Eprenetapopt (APR-246) and Azacitidine in TP53 -Mutant Myelodysplastic Syndromes. J Clin Oncol 39, 1584–1594 (2021).
Li, Y., Buijs-Gladdines, J. G. C. A. M., Canté-Barrett, K., Stubbs, A. P., Vroegindeweij, E. M., Smits, W. K. et al. IL-7 Receptor Mutations and Steroid Resistance in Pediatric T Cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study. PLoS Med 13, e1002200 (2016).
Delgado-Martin, C., Meyer, L. K., Huang, B. J., Shimano, K. A., Zinter, M. S., Nguyen, J. v et al. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia 2017 31:12 31, 2568–2576 (2017).
Senkevitch, E., Hixon, J., Andrews, C., Barata, J. T., Li, W. & Durum, S. The JAK inhibitor ruxolitinib is effective in treating T cell acute lymphoblastic leukemia with gain of function mutations in IL-7R alpha. Blood 126, 1330–1330 (2015).
Cabannes, A., Schmidt, A., Brissot, E., Balsat, M., Maury, S., Isnard, F. et al. The combination of Venetoclax and Tofacitinib Induced Hematological Responses in Patients with Relapse/ Refractory T-ALL with BCL2 Expression and Surface IL7R Expression or IL7R-Pathway Mutations (On Behalf of the GRAALL). Blood 134, 1339 (2019).