OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press59910.17650/1818-8346-2022-17-4-166-176BASIC RESEARCHФУНДАМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ В ПРАКТИЧЕСКОЙ МЕДИЦИНЕ НА СОВРЕМЕННОМ ЭТАПЕMolecular genetic abnormalities in patients with T-cell acute lymphoblastic leukemia: a literature reviewМолекулярно-генетические аномалии у больных Т-клеточными острыми лимфобластными лейкозами: обзор литературыhttps://orcid.org/0000-0003-4316-4833VasilevaA. N.ВасильеваА. Н.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский пр-д, 4

https://orcid.org/0000-0002-9969-8482AleshinaO. A.АлешинаО. А.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский пр-д, 4

https://orcid.org/0000-0002-6253-3334BidermanB. V.БидерманБ. В.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский пр-д, 4

https://orcid.org/0000-0001-9463-9187SudarikovA. B.СудариковА. Б.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский пр-д, 4

National Research Center for Hematology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России071120221741661760711202207112022https://oncohematology.abvpress.ru/ongm/article/view/599

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is an aggressive hematological disease. Modern polychemotherapy protocols allow achieving a 5-year overall survival of 60–90 % in different age groups, however, relapses and refractory forms of T-ALL remain incurable. Over the past decades, the pathogenesis of this variant of leukemia has been studied in many trials, and it has been found that various signaling pathways are involved in the multi-step process of leukemogenesis. This opens the way for targeted therapy.In this review, we provide an update on the pathogenesis of T-ALL, opportunities for introducing targeted therapies, and issues that remain to be addressed.

Т-клеточный острый лимфобластный лейкоз/лимфома (Т-Олл) – агрессивное гематологическое заболевание. Современные протоколы программной комбинированной химиотерапии позволяют достичь 5-летней общей выживаемости 60–90 % в разных возрастных группах, однако рецидивы и рефрактерные формы Т-Олл остаются некурабельными ситуациями. За последние десятилетия было проведено множество исследований, направленных на изучение патогенеза этого варианта лейкоза, и обнаружено, что в многоступенчатом процессе лейкемогенеза задействованы различные сигнальные пути. это открывает перспективы для таргетной терапии.В настоящем обзоре мы предоставляем обновленную информацию о патогенезе T-Олл, возможностях для внедрения таргетной терапии и проблемах, которые еще предстоит решить.

acute lymphoblastic leukemiamolecular genetic profileNOTCH1острый лимфобластный лейкоз, молекулярно-генетический профиль, NOTCH1Santiago R., Vairy S., Sinnett D. et al. Novel therapy for childhood acute lymphoblastic leukemia. Expert Opin Pharmacother 2017;18(11):1081–99. DOI: 10.1080/14656566.2017.1340938Smith M.A., Seibel N.L., Altekruse S.F. et al. Outcomes for children and adolescents with cancer: challenges for the twenty­first century. J Clin Oncol 2010;28(15):2625–34. DOI: 10.1200/ JCO.2009.27.0421Linabery A.M., Ross J.A. Trends in childhood cancer incidence in the U.S. (1992–2004). Cancer 2008;112(2):416–32. DOI: 10.1002/cncr.23169Key Statistics for Acute Lymphocytic Leukemia (ALL). Available at: https://www.cancer.org/cancer/acute­lymphocytic­leukemia/about/key­statistics.htmlParovichnikova E.N., Troitskaya V.V., Sokolov A.N. et al. Interim results of the Ph­negative acute lymphoblastic leukemia treatment in adult patients (results of Russian research group of ALL treatment (RALL)). Onkogematologiya = Oncohematology 2014;9(3):6–15. (In Russ.). DOI: 0.17650/1818­8346­2014­9­3­6­15Паровичникова Е.Н., Троицкая В.В., Соколов А.Н. и др. Промежуточные результаты по лечению острых Ph­негативных лимфобластных лейкозов у взрослых больных (итоги Российской исследовательской группы по лечению острых лимфобластных лейкозов (RALL)). Онкогематология 2014;9(3):6–15. DOI: 0.17650/1818­8346­2014­9­3­6­15Dores G.M., Devesa S.S., Curtis R.E. et al. Acute leukemia incidence and patient survival among children and adults in the United States, 2001–2007. Blood 2012;119(1):34–43. DOI: 10.1182/blood­2011­04­347872Pui C.H., Robison L.L., Look A.T. Acute lymphoblastic leukaemia. Lancet 2008;371(9617):1030–43. DOI: 10.1016/S0140­6736(08)60457­2Look A.T. Oncogenic transcription factors in the human acute leukemias. Science 1997;278(5340):1059–64. DOI: 10.1126/ science.278.5340.1059Begley C.G., Aplan P.D., Davey M.P. et al. Chromosomal translocation in a human leukemic stem­cell line disrupts the T­cell antigen receptor delta­chain diversity region and results in a previously unreported fusion transcript. Proc Natl Acad Sci USA 1989;86(6):2031–5. DOI: 10.1073/pnas.86.6.2031Mellentin J.D., Smith S.D., Cleary M.L. Lyl­1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix­loop­helix DNA binding motif. Cell 1989;58(1):77–83. DOI: 10.1016/0092­8674(89)90404­2Xia Y., Brown L., Yang C.Y. et al. TAL2, a helix­loop­helix gene activated by the (7;9)(q34;q32) translocation in human T­cell leukemia. Proc Natl Acad Sci USA 1991;88(24):11416–20. DOI: 10.1073/pnas.88.24.11416Royer­Pokora B., Loos U., Ludwig W.D. TTG­2, a new gene encoding a cysteine­rich protein with the LIM motif, is overexpressed in acute T­cell leukaemia with the t(11;14)(p13;q11). Oncogene 1991;6(10):1887–93.Kennedy M.A., Gonzalez­Sarmiento R., Kees U.R. et al. HOX11, a homeobox­containing T­cell oncogene on human chromosome 10q24. Proc Natl Acad Sci USA 1991;88(20):8900–4. DOI: 10.1073/pnas.88.20.8900Bernard O.A., Busson­LeConiat M., Ballerini P. et al. A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. Leukemia 2001;15(10):1495–504. DOI: 10.1038/sj.leu.2402249Ferrando A.A., Neuberg D.S., Staunton J. et al. Gene expression sig­natures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002;1(1):75–87. DOI: 10.1016/s1535­6108(02)00018­1Soulier J., Clappier E., Cayuela J.M. et al. HOXA genes are included in genetic and biologic networks defining human acute T­cell leukemia (T­ALL). Blood 2005;106(1):274–86. DOI: 10.1182/blood­2004­10­3900Liu Y., Easton J., Shao Y. et al. The genomic landscape of pediatric and young adult T­lineage acute lymphoblastic leukemia. Nat Genet 2017;49(8):1211–8. DOI: 10.1038/ng.3909Iacobucci I., Mullighan C.G. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol 2017;35(9):975–83. DOI: 10.1200/ JCO.2016.70.7836Belver L., Ferrando A. The genetics and mechanisms of T cell acute lymphoblastic leukaemia. Nat Rev Cancer 2016;16(8):494–507. DOI: 10.1038/nrc.2016.63Van Vlierberghe P., Pieters R., Beverloo H.B., Meijerink J.P. Molecular­genetic insights in paediatric T­cell acute lymphoblastic leukaemia. Br J Haematol 2008;143(2):153–68. DOI: 10.1111/j.1365­2141.2008.07314.xChiaretti S., Foà R. T­cell acute lymphoblastic leukemia. Haematologica 2009;94(2):160–2. DOI: 10.3324/haematol.2008.004150Bongiovanni D., Saccomani V., Piovan E. Aberrant signaling pathways in T­cell acute lymphoblastic leukemia. Int J Mol Sci 2017;18(9):1904. DOI: 10.3390/ijms18091904Tan T.K., Zhang C., Sanda T. Oncogenic transcriptional program driven by TAL1 in T­cell acute lymphoblastic leukemia. Int J Hematol 2019;109(1):5–17. DOI: 10.1007/s12185­018­2518­zPark S.T., Sun X.H. The Tal1 oncoprotein inhibits E47­mediated transcription. Mechanism of inhibition. J Biol Chem 1998;273(12):7030–7. DOI: 10.1074/jbc.273.12.7030Girardi T., Vicente C., Cools J., De Keersmaecker K. The genetics and molecular biology of T­ALL. Blood 2017;129(9):1113–23. DOI: 10.1182/blood­2016­10­706465Valge­Archer V.E., Osada H., Warren A.J. et al. The LIM protein RBTN2 and the basic helix­loop­helix protein TAL1 are present in a complex in erythroid cells. Proc Natl Acad Sci USA 1994;91(18):8617–21. DOI: 10.1073/pnas.91.18.8617Wadman I., Li J., Bash R.O. et al. Specific in vivo association be­tween the bHLH and LIM proteins implicated in human T cell leukemia. EMBO J 1994;13(20):4831–9. DOI: 10.1002/j.1460­2075.1994.tb06809.xWadman I.A., Osada H., Grütz G.G. et al. The LIM­only protein Lmo2 is a bridging molecule assembling an erythroid, DNA­binding complex which includes the TAL1, E47, GATA­1 and Ldb1/NLI proteins. EMBO J 1997;16(11):3145–57. DOI: 10.1093/emboj/16.11.3145Jurata L.W., Gill G.N. Functional analysis of the nuclear LIM domain interactor NLI. Mol Cell Biol 1997;17(10):5688–98. DOI: 10.1128/MCB.17.10.5688Bach I. The LIM domain: regulation by association. Mech Dev 2000;91(1–2):5–17. DOI: 10.1016/s0925­4773(99)00314­7Grutz G., Forster A., Rabbitts T.H. Identification of the LMO4 gene encoding an interaction partner of the LIM­binding protein LDB1/ NLI1: a candidate for displacement by LMO proteins in T cell acute leukaemia. Oncogene 1998;17(21):2799–803. DOI: 10.1038/sj.onc.1202502Van Vlierberghe P., van Grotel M., Beverloo H.B. et al. The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T­cell acute lymphoblastic leukemia. Blood 2006;108(10):3520–9. DOI: 10.1182/ blood­2006­04­019927Van Vlierberghe P., Ferrando A. The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest 2012;122(10):3398–406. DOI: 10.1172/JCI61269Dear T.N., Sanchez­Garcia I., Rabbitts T.H. The HOX11 gene encodes a DNA­binding nuclear transcription factor belonging to a distinct family of homeobox genes. Proc Natl Acad Sci USA 1993;90(10):4431–5. DOI: 10.1073/pnas.90.10.4431Li L., Zhang J.A., Dose M. et al. A far downstream enhancer for murine Bcl11b controls its T­cell specific expression. Blood 2013;122(6):902–11. DOI: 10.1182/blood­2012­08­447839Andersson E.R., Sandberg R., Lendahl U. Notch signaling: simplicity in design, versatility in function. Development 2011;138(17):3593–612. DOI: 10.1242/dev.063610D’Souza B., Meloty­Kapella L., Weinmaster G. Canonical and non­canonical Notch ligands. Curr Top Dev Biol 2010;92: 73–129. DOI: 10.1016/S0070­2153(10)92003­6Kopan R., Ilagan M.X. The canonical Notch signaling pathway: un­folding the activation mechanism. Cell 2009;137(2):216–33. DOI: 10.1016/j.cell.2009.03.045Heitzler P. Biodiversity and noncanonical Notch signaling. Curr Top Dev Biol 2010;92:457–81. DOI: 10.1016/S0070­2153(10)92014­0Weng A.P., Millholland J.M., Yashiro­Ohtani Y. et al. c­Myc is an important direct target of Notch1 in T­cell acute lymphoblastic leukemia/lymphoma. Genes Dev 2006;20(15):2096–109. DOI: 10.1101/gad.1450406Herranz D., Ambesi­Impiombato A., Palomero T. et al. A NOTCH1­driven MYC enhancer promotes T cell development, trans­formation and acute lymphoblastic leukemia. Nat Med 2014;20(10):1130–7. DOI: 10.1038/nm.3665Palomero T., Lim W.K., Odom D.T. et al. NOTCH1 directly regulates c­MYC and activates a feed­forward­loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci USA 2006;103(48):18261–6. DOI: 10.1073/pnas.0606108103Clappier E., Collette S., Grardel N. et al. NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T­cell acute lymphoblastic leukemia (T­ALL) treated on EORTC trials 58881 and 58951. Leukemia 2010;24(12):2023–31. DOI: 10.1038/leu.2010.205Fryer C.J., White J.B., Jones K.A. Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 2004;16(4):509–20. DOI: 10.1016/j.molcel.2004.10.014Gupta­Rossi N., Le Bail O., Gonen H. et al. Functional interaction between SEL­10, an F­box protein, and the nuclear form of activated Notch1 receptor. J Biol Chem 2001;276(37):34371–8. DOI: 10.1074/jbc.M101343200Oberg C., Li J., Pauley A. et al. The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel­10 homolog. J Biol Chem 2001;276(38):35847–53. DOI: 10.1074/jbc. M103992200O’Neil J., Grim J., Strack P. et al. FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gammasecretase inhibitors. J Exp Med 2007;204(8):1813–24. DOI: 10.1084/jem.20070876Malumbres M., Barbacid M. Mammalian cyclin­dependent kinases. Trends Biochem Sci 2005;30(11):630–41. DOI: 10.1016/j.tibs.2005. 09.005Ettl T., Schulz D., Bauer R.J. The Renaissance of cyclin dependent kinase inhibitors. Cancers (Basel) 2022;14(2):293. DOI: 10.3390/ cancers14020293Weinberg R.A. The retinoblastoma protein and cell cycle control. Cell 1995;81(3):323–30. DOI: 10.1016/0092­8674(95)90385­2Bernt K.M., Hunger S.P. Current concepts in pediatric Philadelphia chromosome­positive acute lymphoblastic leukemia. Front Oncol 2014;4:54. DOI: 10.3389/fonc.2014.00054Hebert J., Cayuela J.M., Berkeley J., Sigaux F. Candidate tumorsuppressor genes MTS1 (p16INK4A) and MTS2 (p15INK4B) display frequent homozygous deletions in primary cells from Tbut not from B­cell lineage acute lymphoblastic leukemias. Blood 1994;84(12):4038–44. DOI: 10.1182/blood.V84.12.4038.bloodjournal84124038Clappier E., Cuccuini W., Cayuela J.M. et al. Cyclin D2 dysregulation by chromosomal translocations to TCR loci in T­cell acute lymphoblastic leukemias. Leukemia 2006;20(1):82–6. DOI: 10.1038/sj.leu.2404008Darnell J.E.Jr. STATs and gene regulation. Science 1997;277(5332):1630–5. DOI: 10.1126/science.277.5332.1630Owen K.L., Brockwell N.K., Parker B.S. JAK­STAT signaling: a double­edged sword of immune regulation and cancer progression. Cancers (Basel) 2019;11(12):2002. DOI: 10.3390/cancers11122002Hu X., Li J., Fu M. et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther 2021;6(1):402. DOI: 10.1038/s41392­021­00791­1Jiang Q., Li W.Q., Aiello F.B. et al. Cell biology of IL­7, a key lymphotrophin. Cytokine Growth Factor Rev 2005;16(4–5):513–33. DOI: 10.1016/j.cytogfr.2005.05.004Mazzucchelli R., Durum S.K. Interleukin­7 receptor expression: intelligent design. Nat Rev Immunol 2007;7(2):144–54. DOI: 10.1038/nri2023Degryse S., Cools J. JAK kinase inhibitors for the treatment of acute lymphoblastic leukemia. J Hematol Oncol 2015;8:91. DOI: 10.1186/s13045­015­0192­7Zhang J., Ding L., Holmfeldt L. et al. The genetic basis of early T­cell precursor acute lymphoblastic leukaemia. Nature 2012;481(7380):157–63. DOI: 10.1038/nature10725De Bock C.E., Cools J. JAK3 mutations and HOXA9 expression are important cooperating events in T­cell acute lymphoblastic leukemia. Mol Cell Oncol 2018;5(3):e1458014. DOI: 10.1080/23723556.2018.1458014Gomez­Pinillos A., Ferrari A.C. mTOR signaling pathway and mTOR inhibitors in cancer therapy. Hematol Oncol Clin North Am 2012;26(3):483–505. DOI: 10.1016/j.hoc.2012.02.014Brown E.J., Albers M.W., Shin T.B. et al. A mammalian protein targeted by G1­arresting rapamycin­receptor complex. Nature 1994;369(6483):756–8. DOI: 10.1038/369756a0Chiu M.I., Katz H., Berlin V. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc Natl Acad Sci USA 1994;91(26):12574–8. DOI: 10.1073/pnas.91.26.12574Sabers C.J., Martin M.M., Brunn G.J. et al. Isolation of a protein target of the FKBP12­rapamycin complex in mammalian cells. J Biol Chem 1995;270(2):815–22. DOI: 10.1074/jbc.270.2.815Hay N., Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18(16):1926–45. DOI: 10.1101/ gad.1212704Jiang B.H., Liu L.Z. Role of mTOR in anticancer drug resistance: perspectives for improved drug treatment. Drug Resist Updat 2008;11(3):63–76. DOI: 10.1016/j.drup.2008.03.001Proud C.G. Signalling to translation: how signal transduction pathways control the protein synthetic machinery. Biochem J 2007;403(2):217–34. DOI: 10.1042/BJ20070024Jastrzebski K., Hannan K.M., Tchoubrieva E.B. et al. Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function. Growth Factors 2007;25(4):209–26. DOI: 10.1080/08977190701779101Krasilnikov M.A., Zhukov N.V. mTOR signaling pathway: a new target for tumor therapy. Sovremennaya onkologiya = Modern Oncology 2010;12(2):9–16. (In Russ.).Красильников М.А., Жуков Н.В. Сигнальный путь mTOR: новая мишень терапии опухолей. Современная онкология 2010;12(2):9–16.Vanhaesebroeck B., Guillermet­Guibert J., Graupera M., Bilanges B. The emerging mechanisms of isoform­specific PI3K signalling. Nat Rev Mol Cell Biol 2010;11(5):329–41. DOI: 10.1038/nrm2882Vadas O., Burke J.E., Zhang X. et al. Structural basis for activation and inhibition of class I phosphoinositide 3­kinases. Sci Signal 2011;4(195):re2. DOI: 10.1126/scisignal.2002165Hawkins P.T., Anderson K.E., Davidson K., Stephens L.R. Signalling through Class I PI3Ks in mammalian cells. Biochem Soc Trans 2006;34(Pt 5):647–62. DOI: 10.1042/BST0340647Guimarães I.S., Tessarollo N.G., Lyra­Júnior P.C. et al. Targeting the PI3K/AKT/mTOR pathway in cancer cells. Updates on Cancer Treatment. Intech Open. DOI: 10.5772/61676Franke T.F., Kaplan D.R., Cantley L.C., Toker A. Direct regulation of the AKT proto­oncogene product by phosphatidylinositol­3,4bisphosphate. Science 1997;275(5300):665–8. DOI: 10.1126/ science.275.5300.665Engelman J.A., Luo J., Cantley L.C. The evolution of phosphatidylinositol 3­kinases as regulators of growth and metabolism. Nat Rev Genet 2006;7(8):606–19. DOI: 10.1038/nrg1879Corvera S., Czech M.P. Direct targets of phosphoinositide 3­kinase products in membrane traffic and signal transduction. Trends Cell Biol 1998;8(11):442–6. DOI: 10.1016/s0962­8924(98)01366­xAlessi D.R., Kozlowski M.T., Weng Q.P. et al. 3­Phosphoinositidedependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. Curr Biol 1998;8(2):69–81. DOI: 10.1016/s0960­9822(98)70037­5Inoki K., Li Y., Zhu T. et al. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002;4(9):648–57. DOI: 10.1038/ncb839Manning B.D., Tee A.R., Logsdon M.N. et al. Identification of the tuberous sclerosis complex­2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3­kinase/akt pathway. Mol Cell 2002;10(1):151–62. DOI: 10.1016/s1097­2765(02)00568­3Kovacina K.S., Park G.Y., Bae S.S. et al. Identification of a prolinerich Akt substrate as a 14­3­3 binding partner. J Biol Chem 2003;278(12):10189–94. DOI: 10.1074/jbc.M210837200Okkenhaug K., Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol 2003;3(4):317–30. DOI: 10.1038/nri1056Palomero T., Sulis M.L., Cortina M. et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T­cell leukemia. Nat Med 2007;13(10):1203–10. DOI: 10.1038/nm1636Silva A., Yunes J.A., Cardoso B.A. et al. PTEN posttranslational in­activation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. J Clin Invest 2008;118(11):3762–74. DOI: 10.1172/JCI34616Schubbert S., Bollag G., Shannon K. Deregulated Ras signaling in developmental disorders: new tricks for an old dog. Curr Opin Genet Dev 2007;17(1):15–22. DOI: 10.1016/j.gde.2006.12.004Tidyman W.E., Rauen K.A. The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr Opin Genet Dev 2009;19(3):230–6. DOI: 10.1016/j.gde.2009.04.001Chiaretti S., Zini G., Bassan R. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis 2014;6(1):e2014073. DOI: 10.4084/MJHID.2014.073Von Lintig F.C., Huvar I., Law P. et al. Ras activation in normal white blood cells and childhood acute lymphoblastic leukemia. Clin Cancer Res 2000;6(5):1804–10.Hagemeijer A., Graux C. ABL1 rearrangements in T­cell acute lymphoblastic leukemia. Genes Chromosomes Cancer 2010;49(4):299–308. DOI: 10.1002/gcc.20743Ferrando A. Can one target T­cell ALL? Best Pract Res Clin Haematol 2018;31(4):361–6. DOI: 10.1016/j.beha.2018.10.001Liu X., Xu Y., Han L., Yi Y. Reassessing the potential of Mybtargeted anti­cancer therapy. J Cancer 2018;9(7):1259–66. DOI: 10.7150/jca.23992Ramsay R.G., Gonda T.J. MYB function in normal and cancer cells. Nat Rev Cancer 2008;8(7):523–34. DOI: 10.1038/nrc2439Thomas M.D., Kremer C.S., Ravichandran K.S. et al. c­Myb is critical for B cell development and maintenance of follicular B cells. Immunity 2005;23(3):275–86. DOI: 10.1016/j.immuni. 2005.08.005Adhikary S., Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 2005;6(8):635–45. DOI: 10.1038/nrm1703Dang C.V. MYC on the path to cancer. Cell 2012;149(1):22–35. DOI: 10.1016/j.cell.2012.03.003Erikson J., Finger L., Sun L. et al. Deregulation of c­myc by translocation of the alpha­locus of the T­cell receptor in T­cell leukemias. Science 1986;232(4752):884–6. DOI: 10.1126/science.3486470Mathieu­Mahul D., Sigaux F., Zhu C. et al. A t(8;14)(q24;q11) translocation in a T­cell leukemia (L1­ALL) with c­myc and TcRalpha chain locus rearrangements. Int J Cancer 1986;38(6):835–40. DOI: 10.1002/ijc.2910380609La Starza R., Borga C., Barba G. et al. Genetic profile of T­cell acute lymphoblastic leukemias with MYC translocations. Blood 2014;124(24):3577–82. DOI: 10.1182/blood­2014­06­578856Liu H., Chi A.W., Arnett K.L. et al. Notch dimerization is required for leukemogenesis and T­cell development. Genes Dev 2010;24(21):2395–407. DOI: 10.1101/gad.1975210Li Q., Pan S., Xie T., Liu H. MYC in T­cell acute lymphoblastic leukemia: functional implications and targeted strategies. Blood Sci 2021;3(3):65–70. DOI: 10.1097/BS9.0000000000000073Takebe N., Nguyen D., Yang S.X. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther 2014;141(2):140–9. DOI: 10.1016/j.pharmthera.2013.09.005