zemirciclib (AZD4573) / AstraZeneca - LARVOL DELTA

PHASE 1B/2A STUDY OF AZD4573 (CDK9I) AND ACALABRUTINIB IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (R/R DLBCL) (ICML 2023) - P1/2 | "AZD4573 + acalabrutinib had manageable safety with no new signals. Clinical activity was promising with durable responses in heavily pretreated pts, including those with prior CAR-T. More mature data will be presented at the conference."

Clinical • P1/2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Antitumor Activity of the Cyclin-Dependent Kinase-9 (CDK9) Inhibitor AZD4573 in Relapsed/Refractory Hematological Malignancies: A Phase 1 First-in-Human Study (ASH 2022) - P1, P1/2 | "AZD4573 had manageable safety and a PK profile suitable for QW dosing in a broad range of hematologic malignancies including lymphoma and leukemia. The reduction in pSer2 and MCL-1 supports the RP2D of 12 mg for lymphoma and 9 mg for leukemia. A combination study of AZD4573 and acalabrutinib (NCT04630756) is ongoing to further examine the DLBCL response signal seen in this study."

Clinical • IO biomarker • P1 data • PK/PD data • Acute Kidney Injury • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Hypotension • Infectious Disease • Leukemia • Liver Failure • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • BCL2 • CDK9

TARGETING HELLS-MCM5 AXIS TO EXPLOIT TRANSCRIPTION-REPLICATION CONFLICTS AS NOVEL THERAPEUTIC STRATEGY IN ANAPLASTIC LARGE CELL LYMPHOMA (EHA 2026) - "Translational impact was assessed through proliferation assays using the selective CDK9 inhibitor AZD4573 and the replicative stress-inducing agent etoposide. By uncoupling these processes, we established a strategic therapeutic window wherein the pharmacological exacerbation of TRCs overwhelms the genome maintenance capacity of cancer cells. These data define a novel therapeutic paradigm for aggressive, "orphan" malignancies like ALCL through the precision targeting of transcriptional and replicative stress."

Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • T Cell Non-Hodgkin Lymphoma • HELLS • MCM5 • PCNA

Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1. (PubMed, Cell Death Dis) - "Only inhibition of CDK9 (by AZD4573 and atuveciclib) or of CDK12/13 (by SR4835 and THZ531)-which target the transcriptional elongation of RNA polymerase II (RNAPII)-exerted a strong apoptotic potential. Because Bcl-2 only inhibits Bax, but not Bak, AZD4573 and SR4835 were able to induce apoptosis in Jurkat cells overexpressing Bcl-2. As tumor cells frequently upregulate Bcl-2, inhibitors of CDK9 and CDK12/13 represent promising anticancer drugs."

IO biomarker • Journal • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2 • BCL2L1 • CDC73 • CDK1 • CDK12 • CDK4 • CDK7 • CDK9 • MCL1

Multitargeted kinase inhibitor LCI139 overcomes chemotherapy resistance in patient-derived non small cell lung cancer organoids by harnessing intrinsic and extrinsic apoptosis (AACR 2026) - "Treatments included LCI139 (0.25-1μM), chemotherapeutics (carboplatin, gemcitabine, pemetrexed, cisplatin), and single-agent inhibitors: PI3K (Buparlisib), CDK4/6 (Ribociclib), CDK9 (AZD4573), AURKA (Barasertib), AURKB (Alisertib). LCI139 demonstrates superior anti-tumor activity versus standard chemotherapeutics in resistant NSCLC through dual activation of intrinsic (cell cycle arrest-induced) and extrinsic (metabolic stress-induced) apoptotic pathways. Efficacy in both cell lines and PTOs validates this micro-physiological platform for drug development, supporting translational potential of multitargeted kinase inhibition for overcoming therapeutic resistance, as aligned with FDA guidance."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • AURKA • AURKB • CASP3 • CASP8 • CASP9 • CDK4 • CDK9

Cyclin-dependent kinase-9 and oxidative phosphorylation inhibition overcome ibrutinib resistance in mantle cell lymphoma. (PubMed, Cancer Res Commun) - "OxPhos inhibitor IACS-010759 demonstrated synergy with AZD4573 in vitro. Thus, CDK9 inhibition exhibits activity in ibrutinib-resistant MCL and can be further enhanced by co-targeting of OxPhos."

Journal • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CDK9 • MCL1 • MYC

Proteomic evaluation of combination data in acute myeloid leukemia to inform mechanism of action and new targets (AACR 2024) - "In the proteomics evaluation study, MOLM13 cells treated for 7 days under different conditions - (1) vehicle control; (2) cytarabine alone; (3) decitabine alone; (4) venetoclax alone; (5) AZD4573 alone; (6) AZD4573+cytarabine; (7) AZD4573+decitabine; (8) AZD4573+venetoclax - were collected for proteomics analysis using LC-MS/MS...Interestingly, targeting AURKB with AZD2811 has been shown to overcome venetoclax resistance in AML... Our proteomics analysis identifies vulnerable and resistant pathways and proteins, shedding light on the mechanism of action and revealing potential new targets for AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AURKB • CDK9 • PHGDH

A novel class of multitarget small molecule PI3K-CDK4/6-CDK9-AURAKA/B inhibitor harnesses Warburg effect against non-small cell lung cancer (AACR 2025) - "Here, we describe how LCI139 harnesses the Warburg effect to induce synthetic lethality in NSCLC. LCI139-sensitive (NCI-H1703) and resistant (NCI-H1781) human NSCLC cells, identified from prior IC50 experiments, were treated with LCI139 (0.25 and 0.5μM) or single agent inhibitors PI3Ki (BKM120), CDK4/6i (Ribociclib), CDK9i (AZD4573), and AURKAi (Alisertib). Multitarget inhibitor, LCI139 is uniquely designed to harness the Warburg effect to induce synthetic lethality in glycolysis-reliant NSCLC by 1) inducing metabolic stress (pAMPK), 2) lowering the threshold to metabolic stress response (FoxO3 stabilization), and 3) enhancing caspase-dependent cell death non-canonical Cas8 activation."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • BAX • BCL2 • BCL2L11 • CDK9 • SLC2A1

Potential novel interventions of oncohistones, epigenetic modifications, and RNA processing machinery in betel-nuts related HNSCC in Taiwan (AACR 2025) - "PI3K/AKT/mTOR interventions, ALK/IGF1R inhibitor, CDK4/6 inhibitor, BCl2 inhibitor, WEE1 inhibitor, ATR inhibitor, DNA-PK inhibitor, AT2AR inhibitor, Mcl-1 inhibitor, MEK1/2 inhibitor, JAK2 inhibitor, CXCR4 inhibitor, FAK inhibitor, p53 reactivator, MDM2 inhibitor, SHP2 inhibitor, PARP7 inhibitor, IAP inhibitor, GLS1 inhibitor, eribulin, & VEGFR2/ PDGFR/FGFR or VEGFR2/c-MET/Axl triple blockage might be effective on TW2.6 and reverse treatment refractoriness, through the inhibition of mesenchymal transformation, pRB, & PI3K/AKT /mTOR signaling and modulation of stemness & PD1/PDL1 pathway...Disrupting NSD1 in HNSCC cell lines led to CpG hypomethylation & enhanced cisplatin sensitivity. TW2.6 used to test (1)in vitro drug sensitivity to (a)Chemical Modulators of Splicing; (b)PRMT5 inhibitor; (c)CDK9 inhibitor, EZH2i, DNMT3i, BRD/BET4i, and HDACi; (d)NSD1/SETD2 inhibitor; (e)METTL3 inhibitor; (2)synergistic effects with other therapies by MTT assay, colony..."

IO biomarker • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • AKT1 • ALK • ARID1B • ATM • AXL • BRD4 • CCND3 • CDK12 • CXCR4 • DDR2 • EPHB1 • FAT1 • FGF10 • FGFR • FLCN • HRAS • KDM5A • KDR • METTL3 • MITF • NSD1 • PDGFRB • PIK3CA • RICTOR • RPS6KB1 • SDHA • SETD2 • SOX9 • STK11 • TERT • TIPARP • TMB • TNFAIP3

Organoid-based drug screening identifies CDK9 as a target for stratified treatment of high-grade serous ovarian cancer (AACR 2025) - "To explore the CDK9i responses in HGSC, we profiled 18 organoid cultures against selective CDK9i (AZD4573, VIP-152, NVP-2 and KB-0742). For instance, expression of phosphodiesterase 3B (PDE3B) was correlated with CDK9i resistance (Pearson r = -0.744, p<0.001), while expression of ERBB3 was correlated with increased CDK9i sensitivity (Pearson r = 0.841, p<0.0001).Taken together, we demonstrate the application of an HGSC organoid biobank for identifying patient-specific targets, exceptional responder groups and potential CDK9i sensitivity biomarkers in HGSC. Results of this project could serve as a basis for designing a molecularly stratified CDK9 inhibitor-focused clinical trial in refractory HGSC patients."

High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CDK9 • ERBB3 • MYC

In silico design of novel multitarget small molecule inhibitor LCI139 for the treatment of PTEN-mutant endometrial carcinoma (AACR 2024) - "Triple PI3K-CDK4/6-CDK9 inhibitor, LCI139, is nanomolar potent against PTEN mutant EC cell lines and displays decreased toxicity compared with CDK9 inhibitor reference compounds, AZD4573 and flavopiridol. Our results merit further mechanistic dissection of PTEN interaction with PI3K pathway signaling, cell cycle machinery, CDK9-mediated transcriptional control. These data support extensive in vivo potency, toxicity, PK/PD studies to assess LCI139's clinical utility in treating EC."

Endometrial Cancer • Oncology • Solid Tumor • ANXA5 • CDK6 • MCL1 • PIK3CA • PIK3CD • PIK3CG • PTEN

CDK9 inhibitors modulate the transcriptional landscape of colorectal cancer to suppress MAPK signaling and synergizes with BRAF inhibitors to treat BRAF-mutant colorectal cancer (AACR 2024) - "Cyclin-dependent kinase 9 (CDK9) is a key activator of RNA Pol II transcription and promotes the expression of many cancer driver genes, making CDK9 a promising target for cancer therapy. Human CRC cell lines, patient-derived organoids (PDOs), cell line xenografts, and patient-derived xenografts were used to investigate the efficacy and mechanisms of action of the CDK9 inhibitors AZD4573, enitociclib, and NVP-2, as well as the BRAF inhibitors encorafenib and dabrafenib. We have found CDK9 inhibitors to potently suppress CRC growth and survival through a unique mechanism of action, by vertical suppression of the MAPK signaling pathway. We demonstrate that CDK9 inhibitors can synergize with BRAF inhibitors in the treatment of BRAF-mutant CRC models. Thus, CDK9 inhibitors are a promising class of drugs warranting further investigation, including early-phase clinical trials, in mCRC."

Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor • EGFR • KRAS • MYC

Clinical metabolomics reveals baseline biomarkers of hepatic dysfunction correlating with irregular drug-induced ALT and bilirubin elevations (AACR 2024) - "AZD4573 is a highly potent and selective Cyclin-Dependent Kinase 9 inhibitor...Dosing patients already experiencing higher liver stress levels may be more susceptible to drug-induced ALT and bilirubin elevation, and patients with increasing in-study liver stress may only present at later doses. This work demonstrates metabolomics utility to elucidate possible mechanisms of liver toxicity as well as to identify potential predictive biomarkers for further investigation to explore individual patient risk in clinical studies."

Biomarker • Clinical • First-in-human • Oncology • CDK9

Targeting CDK9 in cutaneous T-cell lymphoma using patient-derived xenograft models (AACR 2024) - "In addition, the expression level of MCL-1 appeared to be correlated with the ex vivo anti-tumor activity of AZD4573. Our findings provide a rationale for clinical investigation of targeting CDK9 in CTCL."

Preclinical • Cutaneous T-cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • ANXA5 • CASP3 • CASP7 • CD2 • CDK9 • MCL1

AZD4573 in combination with CHOP increases combination benefit in preclinical peripheral T-cell lymphoma models (AACR 2024) - "Using MCL-1 inhibitor AZD5991, we showed statistically significant benefit in survival when combined with CHOP in MCL-1 dependent preclinical pTCL PDX models (Koch et al. CHOP treatment in vitro resulted in a decrease in c-MYC levels but not MCL-1, suggesting that combination benefit may be driven through c-MYC. This data suggests that treatment with AZD4573 as a monotherapy or in combination with CHOP regimen ­would be an effective therapeutic strategy in pTCL."

Combination therapy • IO biomarker • Preclinical • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • BCL2 • BCL2A1 • BCL2L1 • CASP3 • CASP7 • MYC

Application of high-grade serous ovarian cancer organoids in functional precision medicine (AACR 2024) - "In several patients, we observed a pronounced cytotoxicity of several cyclin-dependent kinase (CDK) inhibitors, all of which potently inhibit CDK9, including two selective inhibitors (AZD4573 and VIP152) in clinical development. A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids. Developmental Cell (2023)"

Hematological Malignancies • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2

Targeting CDK9 with a novel potent and selective inhibitor, YX0798, in CAR-T-relapsed mantle cell lymphoma models (AACR 2024) - "Targeting CDK9 with its inhibitors AZD4573 and enitociclib is safe and effective for treatment in preclinical MCL models, and they are currently under clinical investigation to assess their efficacy and safety. This treatment efficacy was found to be similar at that of AZD4573 but at a higher dosage (15+15 mg/kg, 2 hours split, QW, IP). No adverse effects in mice were observed for any of treatments.ConclusionThese data show that our novel CDK9 inhibitor YX0798 is potent and efficacious in treating aggressive MCL models and overcame CAR-T resistance at a lower dosage than AZD4573."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • CDK9 • MCL1 • MYC

Drug discovery of potent and specific CDK9 protein degraders for the treatment of refractory lymphomas (AACR 2025) - "To construct CDK9 PROTACs, we adopted our identified CDK9is, clinical candidates AZD4573 and VIP152, conjugating with E3 ligands via diverse linkers for comparison studies. Through rational drug design and structure-based chemical optimization, YX0798 was discovered as a novel CDK9i with high binding affinity, cellular potency, target specificity, and favorable PK properties. Several promising potent and specific CDK9 degraders such as YX0597 have been identified. YX0597 is a bona fide CDK9 degrader highly effective against various resistant MCL cells, induces cell apoptosis and suppresses the tumor growth in vivo at a very low dosage in a PDX mouse model with dual resistance to BTKi and CAR-T, indicating its potential for the treatment of refractory lymphomas including resistant MCL."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CASP3 • CDK9 • MCL1 • MYC

Preclinical activity of investigational menin inhibitor DSP-5336 (Enzomenib)-based combinations against MLL1-rearranged (MLL-r) or mutant-NPM1 AML models (ASH 2025) - "Previously reported preclinical data showed that treatment with Menin inhibitor (MI),e.g., SNDX-5613 (revumenib) or KO-539 (ziftomenib), disrupts binding of Menin to MLL1/2 and MLL1-FP,leading to reduced MLL1/2 and MLL1-FP target gene expression, as well as induction of differentiationand apoptosis in AML cells expressing MLL-FP or mtNPM1c...Notably, in the cell lines and PD AML cells with MLLr ormtNPM1c AML, in vitro treatment with DSP-5336 in combination with CDK9 inhibitor (CDK9i) AZD4573 orBAY1251152 for 48 to 96 hours induced synergistic apoptosis or loss of viability, as discovered by the ZIPmethod with SynergyFinder...In vivo co-treatment with DSP-5336 and BAY1251152 showedsignificantly greater reduction in AML burden than treatment with each agent alone (p< 0.05), withoutinducing weight loss or other toxicities. These preclinical findings underscore the anti-AML activity of DSP-5336 and its molecular correlates, aswell as demonstrate synergistic in vitro and..."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • BCL2 • CASP3 • CD123 • CD33 • CD99 • CDK6 • CLEC12A • FLT3 • HOXA9 • IFNG • IL3RA • ITGAM • KMT2A • MEF2C • MEIS1 • NPM1 • PBX3

CDK9 Inhibition Overcomes Ibrutinib Resistance in Mantle Cell Lymphoma (MCL) (ASH 2023) - "IACS-010759, an inhibitor of complex I of the ETC which targets OxPhos, demonstrated synergy with AZD4573 in parental and ibr-resistant MCL cell lines. CDK9 inhibition with AZD4573 induced apoptosis, downregulated MYC and MCL1 and NFκB signaling, and overcame ibr resistance in preclinical MCL models. This was also noted in a sample obtained from a clinical trial. Prolonged CDK9 inhibition led to metabolic reprogramming towards OxPhos, which thus can serve as a therapeutic target in MCL."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CD40LG • CD5 • MYC • PTPRC • TGFB1 • TNFA

The Novel CDK9/CDK4/6/PI3K Triple Inhibitor LCI139 for the Treatment of MYC-Driven Mantle Cell Lymphoma (ASH 2023) - "Compared with clinical single agent CDK9 inhibitor AZD4573, LCI139 is less toxic to normal human stromal cells (HS-5), whereas both LCI139 and AZD4573 have no significant cytotoxic effect on normal human foreskin fibroblast cells (Hs68). Finally, we show that LCI139 overcomes chronic ibrutinib resistance by decreasing viability in JeKO-1 IR and Mino IR cells with an IC50 of 79 nM and 89 nM, respectively. Therefore, the multitarget small molecule inhibitor LCI139 has superior potency against IR MCL cell lines and overcomes ibrutinib-resistance at nanomolar doses."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • ANXA5 • CCND1 • CDK9 • MYC • PARP1 • PIK3CA • PIK3CG

Inhibition of Cyclin-Dependent Kinase 9 Rapidly Induces Apoptosis in Acute Lymphoblastic Leukemia and Shows Synergistic Activity with BH3-Mimetics (ASH 2024) - "Using the multi-CDK inhibitor dinaciclib, which targets CDK1, 2, 5 and 9, and the specific CDK9 inhibitor AZD4573, we analyzed the effects of both inhibitors in a series of ALL cell lines (BCP-ALL n=10, T-ALL n=6) and primary, patient-derived xenograft (PDX) samples (BCP-ALL n=15, T-ALL n=9)...Based on this, we investigated combinatorial inhibition of CDK9 (AZD4573) together with inhibitors of BCL-2 or BCL-XL (venetoclax, A-1331852, AZD4320) using dose-response matrix analyses and found enhanced cell death and synergistic activity for both combinations...However, intrinsic insensitivity due to dysbalanced protein levels of pro-survival proteins might limit efficacy. Combining CDK9 inhibition with inhibitors of the anti-apoptotic molecules BCL-2/BCL-XL significantly enhances cell death, thus overcoming insensitivity and providing an effective, novel therapeutic anti-ALL strategy to be further evaluated for clinical application."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ANXA5 • BCL2L1 • CASP3 • CDK1 • CDK9 • MCL1

AZD4573 in Combination with CHOP Increases Combination Benefit in Preclinical Peripheral T-Cell Lymphomas Models (ASH 2023) - P2 | "Current standard of care for pTCL revolves around the chemotherapy regimens CHOP/E and for CD30-postive pTCLs, brentuximab vedotin is approved...Using the MCL-1 inhibitor AZD5991, we have shown statistically significant benefit in survival when combined with CHOP in 2 MCL-1 dependent preclinical pTCL PDX models (Koch et al...These data suggested that treatment with AD4573 either as a monotherapy or in combination with CHOP, would be an effective therapeutic strategy in pTCL. AZD4573 monotherapy is currently being evaluated in a phase 2 study (NCT05140382) to assess the efficacy, safety, and PK in patients with relapsed/refractory pTCL."

Combination therapy • IO biomarker • Preclinical • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • BCL2 • BCL2A1 • BCL2L1 • CASP3 • CASP7 • MYC • TNFRSF8

Variable Response of MLL-Rearranged Leukemia Cell Lines to Combinations of Menin, CDK9 and DOT1L Inhibitors (ASH 2023) - " We performed cell viability experiments on leukemia cell lines (MV4; 11, MOLM13, RS4; 11, THP1, SEM, KOPN8, NOMO1, HL60, ML2) with single, two and three drug combinations using a menin inhibitor (VTP50469), a DOT1L inhibitor (EPZ5676), and a CDK9 inhibitor (AZD4573). Based on our preclinical in vitro findings, the co-inhibition of menin-DOT1L or menin-CDK9 is a promising approach for the treatment of MLL-r leukemia. The varying responses of different MLL-r leukemia cell lines to drug combination treatment indicate that not all cases of MLL-r leukemia will respond uniformly to treatment combinations. Taken together, our data provide a strategy to determine optimal treatment combinations for personalized treatment of MLL-r leukemia."

Preclinical • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CDK9 • DOT1L • GLI2 • ITGAM • KMT2A

Transient CDK9 Inhibition with AZD4573 Effectively Induces Apoptosis in Burkitt Lymphoma As a Monotherapy in Pre-Clinical Models (ASH 2023) - P2 | "AZD4573 is currently in a phase 2 study (NCT05140382) to assess the efficacy, safety, and PK of AZD4573 in patients with relapsed or refractory Peripheral T-cell lymphomas (pTCL). Our findings demonstrate that targeting CDK9 with AZD4573 can effectively induce apoptosis in pre-clinical BL models and could be an effective therapy for BL patients."

Monotherapy • Preclinical • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • BCL2 • BCL2L1 • CASP3 • MCL1 • MYC