Journal of Shanghai Jiao Tong University (Medical Science) >
Research progress in targeted therapies of chronic lymphocytic leukemia
Received date: 2023-09-18
Accepted date: 2023-12-07
Online published: 2024-02-28
Supported by
Hebei Province Medical Science Research Program(20230330)
Chronic lymphocytic leukemia (CLL) is one of small B-cell lymphomas and leukemias, characterized as a clonal disease of mature B cells. The disease is remarkably heterogeneous, with the majority of patients having an indolent course, yet they are currently incurable. Abnormal signaling pathways are indispensable in the pathogenesis of CLL. In CLL, the common abnormalities of signaling pathways include B-cell receptor (BCR) signaling, apoptosis, nuclear factor kappa B (NF-κB) signaling and Notch signaling. According to the target in signaling pathways, a series of targeted drugs, such as Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, zanubrutinib), phosphorylate phosphoinositide 3-kinase (PI3K) inhibitor (duvelisib) and B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax), which have significantly changed the prognosis of patients in clinic. Other targeted drugs, such as fenebrutinib, nemtabrutinib and umbralisib, as well as chimeric antigen receptor T-cell (CAR-T) therapy developed in the field of immuno-oncology and T cell engineering, are currently under trial, with more personalized treatment modalities being explored, which may become potential drug targets in the future. In this paper, relevant literature of CLL was reviewed, and recent research progress in molecular pathogenesis and targeted therapies of chronic lymphocytic leukemia was reviewed.
Yanling DING , Jie LI , Jun YUAN , Yan LI . Research progress in targeted therapies of chronic lymphocytic leukemia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024 , 44(2) : 264 -270 . DOI: 10.3969/j.issn.1674-8115.2024.02.013
| 1 | HALLEK M, AL-SAWAF O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures[J]. Am J Hematol, 2021, 96(12): 1679-1705. |
| 2 | PUTOWSKI M, GIANNOPOULOS K. Perspectives on precision medicine in chronic lymphocytic leukemia: targeting recurrent mutations-NOTCH1, SF3B1, MYD88, BIRC3[J]. J Clin Med, 2021, 10(16): 3735. |
| 3 | PETRACKOVA A, TURCSANYI P, PAPAJIK T, et al. Revisiting Richter transformation in the era of novel CLL agents[J]. Blood Rev, 2021, 49: 100824. |
| 4 | ALMASRI M, AMER M, GHANEJ J, et al. Druggable molecular pathways in chronic lymphocytic leukemia[J]. Life, 2022, 12(2): 283. |
| 5 | AGATHANGELIDIS A, CHATZIDIMITRIOU A, GEMENETZI K, et al. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL[J]. Blood, 2021, 137(10): 1365-1376. |
| 6 | SHORER ARBEL Y, BRONSTEIN Y, DADOSH T, et al. Spatial organization and early signaling of the B-cell receptor in CLL[J]. Front Immunol, 2022, 13: 953660. |
| 7 | DELGADO J, NADEU F, COLOMER D, et al. Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies[J]. Haematologica, 2020, 105(9): 2205-2217. |
| 8 | MEIER-ABT F, LU J Y, CANNIZZARO E, et al. The protein landscape of chronic lymphocytic leukemia[J]. Blood, 2021, 138(24): 2514-2525. |
| 9 | LóPEZ-OREJA I, PLAYA-ALBINYANA H, ARENAS F, et al. Challenges with approved targeted therapies against recurrent mutations in CLL: a place for new actionable targets[J]. Cancers, 2021, 13(13): 3150. |
| 10 | POZZO F, BITTOLO T, TISSINO E, et al. Multiple mechanisms of NOTCH1 activation in chronic lymphocytic leukemia: Notch1 mutations and beyond[J]. Cancers, 2022, 14(12): 2997. |
| 11 | AL-SAWAF O, FISCHER K. TP53 mutations in CLL: does frequency matter?[J]. Blood, 2021, 138(25): 2600-2601. |
| 12 | ALBI E, CAPASSO A, SCHIATTONE L, et al. Are we finally getting personal? Moving towards a personalized approach in chronic lymphocytic leukemia[J]. Semin Cancer Biol, 2022, 84: 329-338. |
| 13 | ROBAK T, WITKOWSKA M, SMOLEWSKI P. The role of bruton's kinase inhibitors in chronic lymphocytic leukemia: current status and future directions[J]. Cancers, 2022, 14(3): 771. |
| 14 | GABALLA S, PINILLA-IBARZ J. BTK inhibitors in chronic lymphocytic leukemia[J]. Curr Hematol Malig Rep, 2021, 16(5): 422-432. |
| 15 | ZAIN R, VIHINEN M. Structure-function relationships of covalent and non-covalent BTK inhibitors[J]. Front Immunol, 2021, 12: 694853. |
| 16 | ABRISQUETA P, LOSCERTALES J, TEROL M J, et al. Real-world characteristics and outcome of patients treated with single-agent ibrutinib for chronic lymphocytic leukemia in Spain (IBRORS-LLC study)[J]. Clin Lymphoma Myeloma Leuk, 2021, 21(12): e985-e999. |
| 17 | REDA G, MATTIELLO V, FRUSTACI A M, et al. Ibrutinib in patients over 80 years old with CLL: a multicenter Italian cohort[J]. Blood Adv, 2023, 7(4): 525-528. |
| 18 | GHIA P, PLUTA A, WACH M, et al. Acalabrutinib versus investigator's choice in relapsed/refractory chronic lymphocytic leukemia: final ASCEND trial results[J]. Hemasphere, 2022, 6(12): e801. |
| 19 | SHARMAN J P, EGYED M, JURCZAK W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-na?ve chronic lymphocytic leukemia[J]. Leukemia, 2022, 36(4): 1171-1175. |
| 20 | BYRD J C, HILLMEN P, GHIA P, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase Ⅲ trial[J]. J Clin Oncol, 2021, 39(31): 3441-3452. |
| 21 | CULL G, BURGER J A, OPAT S, et al. Zanubrutinib for treatment-na?ve and relapsed/refractory chronic lymphocytic leukaemia: long-term follow-up of the phase I/II AU-003 study[J]. Br J Haematol, 2022, 196(5): 1209-1218. |
| 22 | BROWN J R, EICHHORST B, HILLMEN P, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia[J]. N Engl J Med, 2023, 388(4): 319-332. |
| 23 | HUS I, PU?A B, ROBAK T. PI3K inhibitors for the treatment of chronic lymphocytic leukemia: current status and future perspectives[J]. Cancers, 2022, 14(6): 1571. |
| 24 | SK?NLAND S S, BROWN J R. PI3K inhibitors in chronic lymphocytic leukemia: where do we go from here?[J]. Haematologica, 2023, 108(1): 9-21. |
| 25 | JELLOUL F Z, YANG R, GARCES S, et al. Landscape of NOTCH1 mutations and co-occurring biomarker alterations in chronic lymphocytic leukemia[J]. Leuk Res, 2022, 116: 106827. |
| 26 | CONDOLUCI A, ROSSI D. Biology and treatment of Richter transformation[J]. Front Oncol, 2022, 12: 829983. |
| 27 | TAUSCH E, SCHNEIDER C, ROBRECHT S, et al. Prognostic and predictive impact of genetic markers in patients with CLL treated with obinutuzumab and venetoclax[J]. Blood, 2020, 135(26): 2402-2412. |
| 28 | PLOUMAKI I, TRIANTAFYLLOU E, KOUMPRENTZIOTIS I A, et al. Bcl-2 pathway inhibition in solid tumors: a review of clinical trials[J]. Clin Transl Oncol, 2023, 25(6): 1554-1578. |
| 29 | ASHOFTEH N, AMINI R, MOLAEE N, et al. MiRNA-mediated knock-down of bcl-2 and mcl-1 increases fludarabine-sensitivity in CLL-CII cells[J]. Asian Pac J Cancer Prev, 2021, 22(7): 2191-2198. |
| 30 | HAFEZI S, RAHMANI M. Targeting BCL-2 in cancer: advances, challenges, and perspectives[J]. Cancers, 2021, 13(6): 1292. |
| 31 | PULLARKAT V A, LACAYO N J, JABBOUR E, et al. Venetoclax and navitoclax in combination with chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia and lymphoblastic lymphoma[J]. Cancer Discov, 2021, 11(6): 1440-1453. |
| 32 | FIORCARI S, MAFFEI R, ATENE C G, et al. Notch2 increases the resistance to venetoclax-induced apoptosis in chronic lymphocytic leukemia B cells by inducing mcl-1[J]. Front Oncol, 2022, 11: 777587. |
| 33 | COCHRANE T, ENRICO A, GOMEZ-ALMAGUER D, et al. Impact of venetoclax monotherapy on the quality of life of patients with relapsed or refractory chronic lymphocytic leukemia: results from the phase 3b VENICE Ⅱ trial[J]. Leuk Lymphoma, 2022, 63(2): 304-314. |
| 34 | SHAO X Y, MENG X Q, YANG H P, et al. IFN-γ enhances CLL cell resistance to ABT-199 by regulating MCL-1 and BCL-2 expression via the JAK-STAT3 signaling pathway[J]. Leuk Lymphoma, 2023, 64(1): 71-78. |
| 35 | FANG Z L, MENG Q C, XU J, et al. Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives[J]. Cancer Commun, 2023, 43(1): 3-41. |
| 36 | HASELAGER M, THIJSSEN R, WEST C, et al. Regulation of Bcl-XL by non-canonical NF-κB in the context of CD40-induced drug resistance in CLL[J]. Cell Death Differ, 2021, 28(5): 1658-1668. |
| 37 | FABBRI G, DALLA-FAVERA R. The molecular pathogenesis of chronic lymphocytic leukaemia[J]. Nat Rev Cancer, 2016, 16(3): 145-162. |
| 38 | QUIJADA-áLAMO M, HERNáNDEZ-SáNCHEZ M, RODRíGUEZ-VICENTE A E, et al. Biological significance of monoallelic and biallelic BIRC3 loss in del(11q) chronic lymphocytic leukemia progression[J]. Blood Cancer J, 2021, 11(7): 127. |
| 39 | VISENTIN A, MAURO F R, CIBIEN F, et al. Continuous treatment with Ibrutinib in 100 untreated patients with TP53 disrupted chronic lymphocytic leukemia: a real-life campus CLL study[J]. Am J Hematol, 2022, 97(3): E95-E99. |
| 40 | HAMPEL P J, PARIKH S A. Chronic lymphocytic leukemia treatment algorithm 2022[J]. Blood Cancer J, 2022, 12(11): 161. |
| 41 | MORABITO F, DEL POETA G, MAURO F R, et al. TP53 disruption as a risk factor in the era of targeted therapies: a multicenter retrospective study of 525 chronic lymphocytic leukemia cases[J]. Am J Hematol, 2021, 96(8): E306-E310. |
| 42 | BOMBEN R, ROSSI F M, VIT F, et al. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: a campus CLL study[J]. Leukemia, 2023, 37(4): 914-918. |
| 43 | BOMBEN R, ZUCCHETTO A, POZZO F, et al. TP53 mutations and clinical outcome in chronic lymphocytic leukemia: is a threshold still needed?[J]. Hemasphere, 2023, 7(4): e855. |
| 44 | COOMBS C C, EASAW S, GROVER N S, et al. Cellular therapies in chronic lymphocytic leukemia and richter's transformation: recent developments in chimeric antigen receptor T-cells, natural killer cells, and allogeneic stem cell transplant[J]. Cancers, 2023, 15(6): 1838. |
| 45 | ABBASI S, TOTMAJ M A, ABBASI M, et al. Chimeric antigen receptor T (CAR-T) cells: novel cell therapy for hematological malignancies[J]. Cancer Med, 2023, 12(7): 7844-7858. |
| 46 | SIDDIQI T, SOUMERAI J D, DORRITIE K A, et al. Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL[J]. Blood, 2022, 139(12): 1794-1806. |
| 47 | KHARFAN-DABAJA M A, YASSINE F, GADD M E, et al. Driving out chronic lymphocytic leukemia with CAR T cells[J]. Transplant Cell Ther, 2022, 28(1): 5-17. |
| 48 | GILL S, VIDES V, FREY N V, et al. Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia[J]. Blood Adv, 2022, 6(21): 5774-5785. |
| 49 | LUO Y, QIE Y Q, GADD M E, et al. Translational development of a novel BAFF-R CAR-T therapy targeting B-cell lymphoid malignancies[J]. Cancer Immunol Immunother, 2023, 72(12): 4031-4047. |
/
| 〈 |
|
〉 |