<i>ZNF384</i>
            -related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype

Hirabayashi, Shinsuke; Ohki, Kentaro; Nakabayashi, Kazuhiko; Ichikawa, Hitoshi; Momozawa, Yukihide; Okamura, Koji; Yaguchi, Akinori; Terada, Kazuki; Saito, Yuya; Yoshimi, Ai; Ogata‐Kawata, Hiroko; Sanada, Hiromi; Kato, Motohiro; Fujimura, Junya; Hino, Moeko; Kinoshita, Akitoshi; Kakuda, Harumi; Kurosawa, Hidemitsu; Kato, Keisuke; Kajiwara, Ryosuke; Moriwaki, Koichi; Morimoto, Takahiro; Nakamura, Kozue; Noguchi, Yasushi; Osumi, Tomoo; Sakashita, Kazuo; Takita, Junko; Yuza, Yuki; Matsuda, Koich; Yoshida, Teruhiko; Matsumoto, Kenji; Hata, Kenichiro; Kubo, Michiaki; Matsubara, Yoichi; Fukushima, Takashi; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira; Kiyokawa, Nobutaka

doi:10.3324/haematol.2016.151035

Cited by 178 publications

(185 citation statements)

References 28 publications

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“…At least eight different ZNF384 fusion partners have been reported to date . While as a group ALLs with ZNF384 fusions show standard risk features, some studies suggest that the cases with the TCF3‐ ZNF384 fusion may be characterized by higher cell counts, younger age at presentation, significantly poorer steroid response, and a higher frequency of relapse …”

Section: Discussionmentioning

confidence: 99%

Myeloid lineage switch following chimeric antigen receptor T‐cell therapy in a patient with TCF3‐ZNF384 fusion‐positive B‐lymphoblastic leukemia

Oberley

Gaynon

Bhojwani

et al. 2018

Pediatric Blood & Cancer

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A pediatric patient diagnosed initially with B-lymphoblastic leukemia (B-ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T-cell (CAR-T) therapy and hematopoietic stem cell transplant. A TCF3-ZNF384 fusion was identified at diagnosis, persisted through B-ALL relapse, and was also present in the AML relapse cell population. ZNF384-rearrangements define a molecular subtype of B-ALL characterized by a pro-B-cell immunophenotype; furthermore, ZNF384-rearrangements are prevalent in mixed-phenotype acute leukemias. Lineage switch following CAR-T therapy has been described in patients with KMT2A (mixed lineage leukemia) rearrangements, but not previously in any patient with ZNF384 fusion.

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Section: Discussionmentioning

confidence: 99%

Myeloid lineage switch following chimeric antigen receptor T‐cell therapy in a patient with TCF3‐ZNF384 fusion‐positive B‐lymphoblastic leukemia

Oberley

Gaynon

Bhojwani

et al. 2018

Pediatric Blood & Cancer

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“…On functional analysis, the DUX4 translocation was significantly associated with ETS transcription factor ( ERG ) dysregulation. ZNF, zinc finger protein 384 ( ZNF384 ) translocations were detected with multiple fusion partners, namely, E1A binding protein p300 ( EP300 ) and TCF3 . The clinical features of ZNF384 fusion patients differed according to the fusion partners, and ALL with TCF3‐ZNF384 had a significantly poorer response to steroid and a higher frequency of relapse.…”

Section: Recent Advances In Molecular Biology Of Pediatric Allmentioning

confidence: 99%

Treatment and biology of pediatric acute lymphoblastic leukemia

Kato

Manabe

2018

Pediatrics International

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Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. In the past ALL was intractable but now the survival probability is as high as 80-90%. Improved supportive care, treatment stratification based on relapse risk, biological features of leukemic cells, and optimization of treatment regimens by nationwide and international collaboration have contributed to this dramatic improvement. While including traditional risk factors (e.g. age and leukocyte count at diagnosis), the treatment has been modified based on biological characteristics (aneuploidy and translocation) and treatment response (assessed by minimal residual disease). Treatment for pediatric ALL typically consists of induction therapy with steroids, vincristine, and asparaginase with or without anthracycline, followed by multi-agent consolidation including high-dose methotrexate and re-induction therapy. After consolidation, less intensive maintenance therapy is required for 1-2 years to maintain event-free survival. Recently, using advanced genomic analysis technology, novel sentinel genomic alterations that may provide more precise stratification or therapeutic targets, were identified. Moreover, in the last decade germline variations have been recognized as similarly important contributors to understanding the etiology and sensitivity of ALL to treatment. A more individualized approach based on genomic features (somatic and germline) and treatment response, the introduction of newly developed agents such as molecular targeted drugs or immunotherapy, and social support including long-term follow up are required for further improvement.Key words acute lymphoblastic leukemia, biology, clinical trial, treatment.Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is newly diagnosed in approximately 500 children in Japan annually. A slight male predominance (approx. 1.2-fold higher in boys) has been observed, with a peak incidence at 1-4 years of age. 1 Survival rates were poor 50 years ago, and leukemia was considered to be an intractable disease. Most recent clinical trials, however, have achieved an overall survival probability of 80-90%. The main contributors to this dramatic improvement are the availability of better supportive care, treatment stratification based on relapse risk and the biological features of leukemic cells, and the accumulation of evidence uncovered by clinical trials through nationwide and international collaboration. We herein review the history, current status, and future prospects for the treatment of pediatric ALL, focusing on interventions and biology while excluding infant ALL and relapsed ALL, which have been reported on elsewhere. 2,3

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“…TCF3‐ZNF384 and E‐Z are the most frequent Z‐fusion genes in children and adults respectively. The frequencies of total Z‐fusion genes in Philadelphia chromosome‐negative BCP‐ALL are 4–8% in children and 7% in adults , and we observed an extremely high incidence of the gene, 17%, in adolescents and young adults (15–24 years old) .…”

mentioning

confidence: 59%

“…The ZNF384 gene forms fusion genes with TET family genes, such as the Ewing sarcoma breakpoint region 1 gene (EWSR1) and TATA box‐binding protein‐associated factor 15 (TAF15) , as well as transcription factor 3 (TCF3) , a regulator of B‐cell differentiation . In addition to these findings, we and others recently identified 7 new Z‐fusion genes, including E1A‐binding protein P300 (EP300)‐ZNF384 (E‐Z) and synergin gamma gene (SYNRG)‐ZNF384 (S‐Z) . TCF3‐ZNF384 and E‐Z are the most frequent Z‐fusion genes in children and adults respectively.…”

mentioning

confidence: 89%

ZNF384‐fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities

et al. 2019

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Zinc‐finger protein 384 (ZNF384) fusion (Z‐fusion) genes have recently been identified as recurrent fusion genes in B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) and have been detected in 7–17% of Philadelphia chromosome‐negative BCP‐ALL cases. We selected SALL4 and ID2 as potential Z‐fusion‐specific transcriptional targets that might lead to the differentiation disorder of Z‐fusion‐positive ALL. The introduction of EP300‐ZNF384 and SYNRG‐ZNF384 induced the expression of these genes. Z‐fusion proteins exhibited stronger transcriptional activities on the promoter or enhancer region of these genes than Wild‐Z. Furthermore, GST pull‐down assay revealed that Z‐fusion proteins associated more strongly with EP300 than Wild‐Z. Coexpression of EP300 specifically enhanced the transcriptional activities of Z‐fusion proteins. We propose the increased EP300 binding of Z‐fusion proteins as a mechanism for their increased transcriptional activities.

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ZNF384 -related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype

Cited by 178 publications

References 28 publications

Myeloid lineage switch following chimeric antigen receptor T‐cell therapy in a patient with TCF3‐ZNF384 fusion‐positive B‐lymphoblastic leukemia

Myeloid lineage switch following chimeric antigen receptor T‐cell therapy in a patient with TCF3‐ZNF384 fusion‐positive B‐lymphoblastic leukemia

Treatment and biology of pediatric acute lymphoblastic leukemia

ZNF384‐fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities

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