Last update 01 Nov 2024

CD33 x WT1

Last update 01 Nov 2024

Basic Info

Related Targets

CD33WT1

Drugs associated with CD33 x WT1

WT1/CD33 targets AbTCR-T(Eureka)

Target

CD33 x WT1

Mechanism

CD33 inhibitors [+1]

Active Org.

Memorial Sloan Kettering Cancer Center [+1]

Originator Org.

Eureka Therapeutics, Inc. [+1]

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CD33 x WT1

100 Translational Medicine associated with CD33 x WT1

0 Patents (Medical) associated with CD33 x WT1

Literatures (Medical) associated with CD33 x WT1

11 Jul 2023·Blood Advances

A global study for acute myeloid leukemia with RARG rearrangement

Article

Author: Su, Zhan ; Li, Jian-Hu ; Yu, Yan-Fang ; Zhang, Jing-Ying ; Qin, Ya-Zhen ; Wang, Wei ; Liu, Li-Ping ; Xu, Reng ; Chen, Su-Ning ; Luo, Hong ; Kantarjian, Hagop M. ; Huang, Jin-Yan ; You, M. James ; MacMahon, Suzanne ; Hao, Jian-Ping ; Sanz, Miguel A. ; Wang, Yi ; Such, Esperanza ; Welch, John S. ; Lu, Ying ; Cai, Zhen ; Wen, Li-Jun ; Wang, Huan-You ; Mi, Ying-Chang ; Yan, Xiao-Jing ; Zhang, Le-Ping ; Yuan, Hong-Jian ; Borthakur, Gautam ; Liu, Yong-Jing ; Taussig, David Christopher ; Zhang, Zhang-Lin ; Zhang, Cheng ; Ball, Edward D. ; Zhou, Hong-Sheng ; Jin, Jie ; Du, Xin ; Zhu, Hong-Hu ; Yu, Liang ; Liu, Hong-Xing ; Huang, Rui-Bin ; Hu, Jiong ; Gao, Su-Jun ; Li, Ji ; Chu, Xiao-Xia ; Yin, C. Cameron ; Shen, Shu-Hong ; Zhang, Xin-You

AbstractAcute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

01 Jan 2023·Cancer

Integrated clinical genotype‐phenotype characteristics of early T‐cell precursor acute lymphoblastic leukemia

Article

Author: Yang, Yaling ; Zuo, Zhuang ; Jabbour, Elias J. ; Ye, Matthew T. ; Borthakur, Gautam ; Zhang, Yizhuo ; He, Hua ; You, M. James ; Calin, Steliana ; Wang, Yi ; Tang, Zhenya

AbstractBackgroundEarly T‐cell precursor acute lymphoblastic leukemia (ETP‐ALL) is a distinct subtype of T‐ALL with a unique immunophenotype and high treatment failure rate. The molecular genetic abnormalities and their prognostic impact in ETP‐ALL patients are poorly understood.MethodsThe authors performed systematic analyses of the clinicopathologic features with an emphasis on molecular genetic aspects of 32 patients with ETP‐ALL.ResultsThe median age was 43 years (range, 16–71). The blasts were positive for cytoplasmic CD3 and CD7 and negative for CD1a and CD8. Other markers expressed included CD34 (88%), CD33 (72%), CD117 (68%), CD13 (58%), CD5 (partial, 56%), CD2 (38%), CD10 (25%), CD56 (partial, 19%), and CD4 (6%). Cytogenetic analyses revealed a diploid karyotype in 10 patients, simple (1–2) abnormalities in 10 patients, and complex karyotype in 10 patients. Next‐generation sequencing for 21 patients demonstrated that all had gene mutations (median, four mutations per patient). The most frequently mutated genes were WT1 (38%), NOTCH1 (29%), NRAS (29%), PHF6 (25%), TP53 (24%), ASXL1 (19%), FLT3 (19%), and IKZF1 (19%). All patients except one received multi‐agent chemotherapy, and 22 patients underwent allogeneic stem cell transplantation. Thrombocytopenia, an abnormal karyotype, and TP53 mutation were associated with markedly shortened overall survival. Stem cell transplantation significantly improved overall survival.ConclusionsPatients with ETP‐ALL often have high mutation burden with increased genomic instability. TP53 mutation was the only molecular prognostic marker and was associated with complex karyotype and greater than or equal to five mutations. These patients may benefit from stem cell transplantation, and recurrent gene mutations may be novel therapeutic markers.

06 Jun 2022·World Journal of Clinical Cases

Pediatric acute myeloid leukemia patients with i(17)(q10) mimicking acute promyelocytic leukemia: Two case reports

Author: Ji, A-Duo ; Liu, Yan-He ; Zhang, Wei-Hua ; Wen, Jin-Quan ; Yan, Hong-Xia ; Zhang, Bao-Juan

BACKGROUNDChromosome i(17)(q10) abnormality is mainly associated with chronic myeloid leukemia (CML), myelodysplastic syndrome/myeloproliferative tumors (MDS/MPD), and acute myeloid leukemia (AML). The role of i(17)(q10) in AML is still unknown, the differences between AML and acute promyelocytic leukemia (APL)-like AML with i(17)(q10) need more research. This study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10), similar to APL phenotype.CASE SUMMARYBoth pediatric patients were males; case 1 had newly diagnosed AML, and case 2 showed relapsed tumor after 1 year of drug withdrawal. Bone marrow cell morphology, chromosome karyotype analysis, Fully-instrumented submersible housing test, immunological assays, molecular biological methods, and blood tumor panoramic gene test were performed. All-trans retinoic acid (ATRA) combined with arsenic acid (As2O3) were used in the first course of treatment. Bone marrow was dominated by abnormal promyelocytic granulocytes. Karyotype test revealed i(17)(q10) isochromosome. Immunological phenotype mainly included positive expressions of CD9, CD13, CD33, and CD38. Case 1 suffered intracranial hemorrhage after re-chemotherapy and died on D162. For case 2, on D145 and D265, bone marrow promyelocytic granulocytes accounted for 2%. Flow cytometric residual lesion detection showed no abnormal immunophenotype cells. The copy number of WT1 gene in two cases were 1087 and 1010, respectively, and the expression rates were 55.29% and 59.5%, respectively.CONCLUSIONATRA, As2O3, and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10) but without t(15;17) and PML-RARA fusion gene.

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