Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia

Hosono, Naoko; Yamauchi, Takahiro; Chi, SungGi; Fukushima, Kentaro; Shibayama, Hirohiko; Katagiri, Seiichiro; Gotoh, Akihiko; Eguchi, Motoki; Morishita, Takanobu; Ogasawara, Reiki; Kondo, Takeshi; Yanada, Masamitsu; Yamamoto, Kazuhito; Kobayashi, Tsutomu; Kuroda, Junya; Usuki, Kensuke; Utsu, Yoshikazu; Aotsuka, Nobuyuki; Yoshimitsu, Makoto; Ishitsuka, Kenji; Ono, Takaaki; Takahashi, Naoto; Iyama, Satoshi; Nakamura, Makoto; Nakamura, Yukinori; Fukuhara, Suguru; Izutsu, Koji; Yamauchi, Nobuhiko; Yuda, Junichiro; Minami, Yosuke

doi:10.1182/blood-2021-149960

Cited by 4 publications

(9 citation statements)

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“…Hematologic Malignancy (HM)-SCREEN-Japan-01 (UMIN000035233) is a genome profiling study of patients newly diagnosed with adult AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory (R/R) AML [53][54][55] (methods are described in Supplementary Materials). The objective of the present study was to evaluate the frequency and characteristics of cancer-related genomic alterations in patients with AML using a comprehensive genome profiling assay (FoundationOne ® Heme (F1H)) and to determine the quality of specimens used in gene analysis.…”

Section: Kit Mutation In Unfit and Relapsed/refractory Aml: Results F...mentioning

confidence: 99%

Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

Katagiri

Chi

Minami

et al. 2022

IJMS

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KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients’ prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML.

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Section: Kit Mutation In Unfit and Relapsed/refractory Aml: Results F...mentioning

confidence: 99%

Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

Katagiri

Chi

Minami

et al. 2022

IJMS

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“…This section is composed of a detailed analysis of published data from the Japanese genomic sequencing study HM-SCREEN-Japan 01 [ 111 , 112 ]. Although this study included only a small number of AML patients, it can serve to highlight the characteristics of patients in which conventional treatment was not successful or recommended.…”

Section: Real-world Etiology Of Adverse Genetic Abnormalitiesmentioning

confidence: 99%

“… Detailed analysis of the published data of HM-SCREEN-Japan 01 [ 111 , 112 ]. Among 168 patients whose chromosomal status was known, 63 patients (37.5%) were classified as adverse risk according to the ELN2017 criteria by applying conventional cytogenetic tests only.…”

Section: Figurementioning

confidence: 99%

Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors

Ikeda

Chi

Uchiyama

et al. 2022

IJMS

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The European LeukemiaNet (ELN) criteria define the adverse genetic factors of acute myeloid leukemia (AML). AML with adverse genetic factors uniformly shows resistance to standard chemotherapy and is associated with poor prognosis. Here, we focus on the biological background and real-world etiology of these adverse genetic factors and then describe a strategy to overcome the clinical disadvantages in terms of targeting pivotal molecular mechanisms. Different adverse genetic factors often rely on common pathways. KMT2A rearrangement, DEK-NUP214 fusion, and NPM1 mutation are associated with the upregulation of HOX genes. The dominant tyrosine kinase activity of the mutant FLT3 or BCR-ABL1 fusion proteins is transduced by the AKT-mTOR, MAPK-ERK, and STAT5 pathways. Concurrent mutations of ASXL1 and RUNX1 are associated with activated AKT. Both TP53 mutation and mis-expressed MECOM are related to impaired apoptosis. Clinical data suggest that adverse genetic factors can be found in at least one in eight AML patients and appear to accumulate in relapsed/refractory cases. TP53 mutation is associated with particularly poor prognosis. Molecular-targeted therapies focusing on specific genomic abnormalities, such as FLT3, KMT2A, and TP53, have been developed and have demonstrated promising results.

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“…(HM)-SCREEN-Japan 01 is a multicenter genomic observational study [ 18 , 19 ]. Patients with AML relapsed/refractory to initial therapy or those newly diagnosed but intolerable to standard therapy were recruited.…”

Section: (Hm)-screen-japan 01mentioning

confidence: 99%

“… Detailed analysis of the published data of (HM)-SCREEN-Japan 01 [ 18 , 19 ]: Frequencies of tumor-agnostic variants detected among 177 patients with relapsed/refractory or newly diagnosed unfit AML. TP53 (thirty-seven cases), KIT (fifteen cases), KRAS (twelve cases), BRCA1 (five cases), ATM (four cases), JAK2 (four cases), NTRK3 (one case), FGFR3 (one case) and EGFR (one case) are typical genes for which molecular-targeted drugs have been developed or are under development for solid tumors.…”

Section: Figurementioning

confidence: 99%

Molecular-Targeted Therapy for Tumor-Agnostic Mutations in Acute Myeloid Leukemia

et al. 2022

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Comprehensive genomic profiling examinations (CGPs) have recently been developed, and a variety of tumor-agnostic mutations have been detected, leading to the development of new molecular-targetable therapies across solid tumors. In addition, the elucidation of hereditary tumors, such as breast and ovarian cancer, has pioneered a new age marked by the development of new treatments and lifetime management strategies required for patients with potential or presented hereditary cancers. In acute myeloid leukemia (AML), however, few tumor-agnostic or hereditary mutations have been the focus of investigation, with associated molecular-targeted therapies remaining poorly developed. We focused on representative tumor-agnostic mutations such as the TP53, KIT, KRAS, BRCA1, ATM, JAK2, NTRK3, FGFR3 and EGFR genes, referring to a CGP study conducted in Japan, and we considered the possibility of developing molecular-targeted therapies for AML with tumor-agnostic mutations. We summarized the frequency, the prognosis, the structure and the function of these mutations as well as the current treatment strategies in solid tumors, revealed the genetical relationships between solid tumors and AML and developed tumor-agnostic molecular-targeted therapies and lifetime management strategies in AML.

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Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia

Cited by 4 publications

References 0 publications

Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors

Molecular-Targeted Therapy for Tumor-Agnostic Mutations in Acute Myeloid Leukemia

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