T Acute Lymphoblastic Leukemia

Great talk by @NitinJainMD on T-ALL ➡️ CAR-T cells being optimized with promising results ➡️ Rationale for inhibition of BCL-2 BCL-xl ➡️ LCK in 40% of T-ALL sensitive to dasatinib/ponatinib. Clinical trial at @MDAndersonNews with chemo-VEN-ponatinib #leusm #ALL @_MDEducation (@FadiHaddad_MD)

We provide mechanistic insights into the interplay between signaling and apoptotic pathways. Dual targeting with TKI + BH3 mimetics is synergistic in T-ALL. @myeloidmalig @DrWendyStock (@CanerSaygin)

Thrilled to share our paper, out @CCR_AACR! We showed that LCK and ACK1 pathways drive resistance to BCL2 and BCL-xL inhibition in T-ALL. A collaborative effort with @jl_labelle, @BarbaraLKee, @gvencut1, @Anand_88_Patel, @AyaOncologist and David Teachey. https://t.co/oboxlvYz8r (@CanerSaygin)

Nowy proces produkcyjny może poprawić skuteczność komórek CAR T w leczeniu pacjentów z oporną na leczenie T-ALL. Wzmacnianie poprzez hamowanie - czyli zastosowanie inhibitorów kinazy tyrozynowej w produkcji komórek CAR T - doniesienia z #ASCO23 https://t.co/tvBhM18Byd (@hematoonkologia)

Moving tribute for @pvvlab by @goossens_lab and his contributions to T-ALL field as #EHA2023 David Grimwade award winner. Pieter is sorely missed everyday. (@charles_debock)

R/R T-ALL - is JAKinh+venetoclax or mTOR inh viable options going forward? Drug profiling upfront a powerful tool #EHA2023 #benchtobedside (@horne_gillian)

#ASCO23 #leusm Hill: better expansion and persistence w CD5 CAR-T manuf w TKI wo increased severity of CRS/ICANS (no gr3+). 2 pts developed EBV PLTD. We so badly need a CAR-T for RR T-ALL! Hope this work leads to a successful product. (@hemedoc)

New opportunities for T-ALL including ETP @NitinJainMD #ESHALL2023 (@Junjyang)

Title: DONOR-DERIVED CD5 CAR T CELLS FOR T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA... by Jing Pan EHA Library; Jun 08 2023; 387816 https://t.co/f1SiX3CiYN #EHA23 (@smbenlazar)

β-Catenin and its new partner FOXO3 shake T-ALL | Blood | American Society of Hematology https://t.co/NwIKslYD3M (@syed_abutalibmd)

Alyssa’s CAR T-cell unique combination of anti-CD7 CAR, with TRAC depletion, CD7 depletion and CD52 depletion is a promising treatment for T-ALL. More readily available CAR T- therapies are a reality, also for malignancies beyond B-cell diseases. ⁦ https://t.co/udvXOrPklU (@fabianaperna)

#tandem23 #bmtsm Liang: in T-ALL (small numbers due to rarity) TCRB detection more assoc w relapse, while detection of only TCRG had lower assoc w relapse (but non-negligible). (@hemedoc)

👉👉 Excited to share that our trial of ponatinib (as LCK inhibitor) + VEN + mini-CVD for R/R T-ALL is now open 👉Joint collaboration MDACC and St Jude @Junjyang @jiyang_yu showed 40% T-ALL overexpress LCK and sensitive to ponatinib/dasatinib (Notably, none had ABL fusion) 1/2 (@NitinJainMD)

CD markers simplified CD34+ = Blast CD3+ = T-cell CD19+ = B-cell CD33+ = Myeloid CD34+ = Acute leukemia CD34+ CD19+ = B-ALL CD34+ CD3+ = T-ALL CD34+ CD33+ = AML CD34- CD33+ = APL (promyelocyte differentiated one step above blast) (@AaronGoodman33)

#ASH22 #leusm Saygin: presence of either TP53 or nonTP53 mCH assoc with worse outcomes in B- and T-ALL. (@hemedoc)

Now Dr. Lenk on OSE-127 impact on ALL development #leusm #ash22 -CD127 is implicated in ALL development & expressed in majority of cases -OSE-127 is full antagonist of CD127 -efficacy in PDX B-ALL & T-ALL models as monotherapy & w/ chemo -efficacy driven by ADCP (@Anand_88_Patel)

Any experience in treating T-ALL with NUP214-ABL1 fusion? Was TKI incorporated in therapy ? #medtwitter #hemeonc #MedEd @Satyayadav__ @chepsyphilip @srirajvasudevan @MirghSumeet @lingarajnayak @DrGauravNarula @BijoyTelivala @DrGauravNarula please opine #leusm #lymsm (@faheema_hasan)

Any experience in treating T-ALL with NUP214-ABL1 fusion? Was TKI incorporated in therapy ? #medtwitter #hemeonc #MedEd @Satyayadav__ @chepsyphilip @srirajvasudevan @MirghSumeet @lingarajnayak @DrGauravNarula @BijoyTelivala @DrGauravNarula @ (@faheema_hasan)

Analysis of 53 Patients with Relapsed or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL) Treated with CD7-Targeted CAR-T Cell Therapy https://t.co/A2WYmmajLM #ALL #leusm (@smbenlazar)

I mean even for FPDMM with a germline ASXL1 mutation and nearly 50% risk of AML or T-ALL we don’t prophylactically do alloHCT. (@matthew_mei)

Clusters of Differentiation 2 Tweets! Simplified! CD34+ = Blast CD3+ = T-cell CD19+ = B-cell CD33+ = Myeloid CD34+ = Acute leukemia CD34+ CD19+ = B-ALL CD34+ CD3+ = T-ALL CD34+ CD33+ = AML CD34- CD33+ = APL (promyelocyte differentiated one step above blast) (@AaronGoodman33)

Acute lymphoblastic leukemia hereditary predisposition Familial platelet disorder = RUNX1 -⬇️plt+dysfunction -T-ALL+myeloid Thrombocytopenia 5 = ETV6 -⬇️plt+dysfunction -B-ALL+myeloid PAX5 -B-ALL IKZF1 -Immunodeficiency -B/T-ALL Li-Fraumeni= TP53 -Low hypodiploid ALL+myeloid (@AaronGoodman33)

CD markers for leukemia simplified CD34+ = Blast CD3+ = T-cell CD19+ = B-cell CD33+ = Myeloid CD34+ = Acute leukemia CD34+ CD19+ = B-ALL CD34+ CD3+ = T-ALL CD34+ CD33+ = AML CD34- CD33+ = APL (promyelocyte differentiated one step above blast) CD34- = Mature CD34-CD19+ = CLL (@AaronGoodman33)

#EHA22 #leusm Pölönen: 28% of driver could only be ID’d by whole genome seq. 15 subtypes of T-ALL classifiable based on this analysis. Dataset large enough to ID fav risk (RPL10 mut) & poor risk (LMO2 intergen mut) subgroups. See 4th slide for nice way to show MRD w these data (@hemedoc)

Clinical trial (NCT05268003) investigates combined ponatinib and venetoclax with mini-CVD chemotherapy in pts with R/R T-ALL. Ponatinib (and dasatinib) work by inhibiting LCK enzyme. LCK is over expressed in about 40% T-ALL (no ABL fusions), mostly non-ETP subset @Junjyang (@NitinJainMD)

Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL https://t.co/NBNSeoCZaY (@BloodJournal)

Targeting the #NOTCH1-#MYC-#CD44 axis in leukemia-initiating cells in T-ALL | ⁦@LeukemiaJnl⁩ | Led by .⁦@GBorthakur⁩ & team | ⁦@DrHKantarjian⁩ ⁦@MDAndersonNews⁩ #endcancer #leusm #lymsm #BETi #BRDi #BRD4 https://t.co/HPIFSe9gqz (@doctorpemm)

Sirt1 A Novel Therapeutic Target in T-ALL Daniel Herranz, PharmD, PhD @HerranzLab @RutgersCancer #ASH21 #OlgaLanchoPhD #Sirt1 #ALL #Research https://t.co/a0lHV33My8 (@oncologytube)

A minor modification suggestion, CD34 is not frequently expressed in T-ALL, if flow cyCD3+ smCD3- would work better,... If IHQ, CD3+ TdT+ would also work better than CD34. (@ecoladov)

CD markers simplified per request! CD34+ = Blast CD3+ = T-cell CD19+ = B-cell CD33+ = Myeloid CD34+ = Acute leukemia CD34+ CD19+ = B-ALL CD34+ CD3+ = T-ALL CD34+ CD33+ = AML CD34- CD33+ = APL (promyelocyte differentiated one step above blast) (@AaronGoodman33)

Yang- Cd7 car-t for T-ALL. 4-1bb. Crispr gene editing to prevent fraticide (abs 1696). N=14. 100% manufacture rate. Med 5 line of tx. 93% CR/MRD-ve. 11/13 went to allo. 1 gr3 CRS. No severe ICANS. Med persist 52.5 days. Med Peak by day 15. #ASH21 #leusm #tcell (@hemant_murthy)

#ASH21 #leusm #celltx Lu: CD7 CART in T-ALL. CD28/41BB costim. Assessed impact of selecting or engineering (KO7CAR) CD7neg CART to prevent fratricide vs non-selected (NS7CAR). When NS7CAR used, fratricide selected CD7neg CAR in vivo and NS=K in vitro and xenograft activity (@hemedoc)

Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial https://t.co/EwwV0XJBhk (@hemant_murthy)

Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial https://t.co/OhQ9Rx1yVF (@PLMcCarthyMD)

T-ALL and the talented Mr IL7Rα https://t.co/fM4012jmIL (@BloodJournal)

We have several trials for patients with B-ALL & T-ALL 👉 Frontline trials with chemo + Ino + Blina 👉 Novel mAb (ADCT CD22) 👉 Trials with BCL2 and BCL-xl inhibitors 👉 Allogeneic and autologous #CART CD19 and CD22 targets 👉 Blina + ponatinib and others Email/DM for details (@NitinJainMD)

CD markers simplified CD34+ = Blast CD3+ = T-cell CD19+ = B-cell CD33+ = Myeloid CD34+ = Acute leukemia CD34+ CD19+ = B-ALL CD34+ CD3+ = T-ALL CD34+ CD33+ = AML CD34- CD33+ = APL (promyelocyte differentiated one step above blast) (@AaronGoodman33)

Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase … https://t.co/OGcsTWFMg1 (@PLMcCarthyMD)

90% response rate in this early phase trial for R/R T-cell ALL! #bmtsm #leusm #cartcell #celltherapy Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial https://t.co/uxkSQ3fH5N (@BldCancerDoc)

90% CR rate, impressive results. Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial | Journal of Clinical Oncology https://t.co/K92apBeMIb (@romeerizwan)

This is awesome and makes me happy! CART T-cells for a T-cell malignancy! Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial https://t.co/JQ2exbfO2E (@AaronGoodman33)

Meeting Library | Donor-derived #CD7 CAR T cells for T-cell acute lymphoblastic leukemia | #ASCO21 ⁦@ASCO⁩ | #TcellRx #ImmunoOncology #CART #leusm #lymsm #bmtsm https://t.co/YTdfM4ACJ9 (@doctorpemm)