論文 - 盛武 浩
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Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia 査読あり
Saito Y., Kinoshita M., Yamada A., Kawano S., Liu H.S., Kamimura S., Nakagawa M., Nagasawa S., Taguchi T., Yamada S., Moritake H.
Cancer Science 112 ( 12 ) 4944 - 4956 2021年12月
担当区分：責任著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Science
Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and the TCA cycle, therefore suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene-independent leukemia.
DOI： 10.1111/cas.15138
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Malignant perivascular epithelioid cell neoplasm in the liver: report of a pediatric case. 査読あり
Baba T, Kawano T, Saito Y, Onishi S, Yamada K, Yamada W, Masuya R, Nakame K, Kawasaki Y, Iino S, Sakoda M, Kirishima M, Kaji T, Tanimoto A, Natsugoe S, Ohtsuka T, Moritake H, Ieiri S
Surgical case reports 7 ( 1 ) 212 2021年9月
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Taga T., Tanaka S., Hasegawa D., Terui K., Toki T., Iwamoto S., Hiramatsu H., Miyamura T., Hashii Y., Moritake H., Nakayama H., Takahashi H., Shimada A., Taki T., Ito E., Hama A., Ito M., Koh K., Hasegawa D., Saito A.M., Adachi S., Tomizawa D.
Leukemia 35 ( 9 ) 2508 - 2516 2021年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 95.0% and 96.7% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 98.1% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD with EFS were 14.67 (p = 0.01). Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.
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Yoshikawa N., Yamada A., Yokota T., Yamada Y., Kinoshita M., Moritake H., Ikeda R.
Cancers 13 ( 18 ) 2021年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancers
Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient’s topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.
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Azuma M., Kadota Y., Matsuyama M., Moritake H., Hirai T.
Japanese Journal of Radiology 39 ( 6 ) 564 - 570 2021年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Radiology
Objective: We evaluated the usefulness of fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) imaging for the evaluation of the ectopic posterior pituitary gland (EPPG). Materials and methods: This retrospective study included 9 patients with EPPG due to causes other than tumor. All underwent sagittal two-dimensional (2D) T1W-, FS 3D T1W-VISTA- (VISTA), and 3D T2W-driven equilibrium radiofrequency reset pulse (DRIVE) imaging. Two radiologists independently reviewed the 2D T1W- and VISTA images for their image quality and for visualization of the EPPG and of pituitary stalk transection. DRIVE findings were used as the reference standard for pituitary stalk transection. Interobserver and intermodality agreements were evaluated with the kappa (κ) coefficient. The mean grade assigned to the 2D T1W- and the VISTA imaging technique for visualization of the EPPG was assessed by the Mann–Whitney U test. Results: Interobserver agreement for visualization of the EPPG on 2D T1W- and VISTA images was excellent (κ = 0.82 and κ = 1.00, respectively). The mean grade for EPPG visualization was significantly higher for VISTA- than 2D T1W images (p = 0.0039). Conclusion: FS 3D T1W-VISTA imaging is useful for the evaluation of EPPG. A secondary abstract: Conventional MRI yields insufficient information for the evaluation of the ectopic posterior pituitary gland (EPPG). The visualization of the EPPG was significantly higher for fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) than 2D T1W images. FS 3D T1W-VISTA imaging is useful for the evaluation of the EPPG.
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Aoki T., Takahashi H., Tanaka S., Shiba N., Hasegawa D., Iwamoto S., Terui K., Moritake H., Nakayama H., Shimada A., Koh K., Goto H., Kosaka Y., Saito A.M., Horibe K., Kinoshita A., Tawa A., Taga T., Adachi S., Tomizawa D.
British Journal of Haematology 193 ( 1 ) 176 - 180 2021年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：British Journal of Haematology
The variability in myelosuppression after chemotherapy for acute myeloid leukaemia (AML) can affect its prognosis; however, the underlying mechanism remains controversial. In the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study, we showed that prolonged neutropenia was associated with high overall survival (P = 0·011) and low frequency of relapse (P = 0·042) in patients without granulocyte-colony stimulating factor (G-CSF) who completed the indicated treatment protocol. Our data indicate that predisposition to prolonged neutropenia after chemotherapy is correlated with a better outcome of AML treatment. Our results promote the usage of individualised drug dosing strategies to improve the therapeutic outcome in AML patients.
DOI： 10.1111/bjh.16656
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Yoshikawa N., Yamada A., Yokota T., Moritake H., Hirabara Y., Ikeda R.
Journal of Clinical Laboratory Analysis 35 ( 3 ) e23661 2021年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Laboratory Analysis
Background: The concentration of MTX in blood is often measured quickly and easily by immunoassays. Thus, immunoassays may facilitate the easy determination of the concentration of MTX in the cerebrospinal fluid (CSF). In this study, we measured methotrexate (MTX) concentrations in the CSF using a high-performance liquid chromatography (HPLC) method intended for analyzing CSF matrices and a chemiluminescence immunoassay (CLIA) method intended for assessing serum and plasma matrices and verified the differences in the results of the two methods. Methods: HPLC analysis for MTX in the CSF was performed using a Prominence UFLC system with a C18 column. The HPLC method was validated in accordance with the 2018 FDA guideline. The CLIA method was performed using an ARCHITECT i1000SR system intended for serum and plasma matrices. A total of 47 CSF samples (14 clinical and 33 spiked specimens) were analyzed using the two methods. Results: The HPLC method passed the validation criteria. The concentration of MTX in the same sample, determined using the HPLC and CLIA methods, differed proportionally; the percent difference in the concentrations averaged −23.0% (95% confidence interval: −36.9% to −9.1%) as revealed by the Bland-Altman plot. The relationship between the measured values, evaluated using the Passing-Bablok regression, was as follows: HPLC = 1.205 × CLIA – 0.024. Conclusion: The equation deduced in this study can be used to correct the concentration of MTX measured using the CLIA method.
DOI： 10.1002/jcla.23661
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A useful method to diagnose Pearson syndrome mimicking Diamond–Blackfan anemia 査読あり
Nishimura T., Yamada A., Utoyama M., Saito Y., Moritake H.
Pediatrics International 63 ( 2 ) 223 - 225 2021年2月
担当区分：責任著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pediatrics International
DOI： 10.1111/ped.14385
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Moritake H., Tanaka S., Miyamura T., Nakayama H., Shiba N., Shimada A., Terui K., Yuza Y., Koh K., Goto H., Kakuda H., Saito A., Hasegawa D., Iwamoto S., Taga T., Adachi S., Tomizawa D.
Pediatric Blood and Cancer 68 ( 1 ) e28736 2021年1月
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pediatric Blood and Cancer
Background: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation (HCT) as a second-line therapy and improvements in supportive care following anthracycline- and cytarabine-based chemotherapy; however, the outcomes of children with relapsed AML still remain unsatisfactory. Procedure: In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients who relapsed after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol and who were registered in the retrospective JPLSG AML-05R study. Results: The 5-year overall survival rate was 36.1%. The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the nonsurviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (P <.01). Moreover, achieving a second complete remission (CR2) prior to HCT was associated with a good prognosis (P <.01). Etoposide, cytarabine, and mitoxantrone (ECM)- or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (P <.01). A genetic analysis also revealed the prognostic significance of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication as a poor prognostic marker (P =.04) and core binding factor-AML, t(8;21), and inv(16) as good prognostic markers (P <.01). Conclusions: Achieving a CR2 prior to HCT is important in order to improve the prognosis of relapsed pediatric AML. Recent molecular targeted therapies, such as FLT3 inhibitors, may contribute to overcome their prognoses. Larger prospective investigations are necessary to establish individualized treatment strategies for patients with relapsed childhood AML.
DOI： 10.1002/pbc.28736
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パゾパニブが有効性を示した多発肺転移を有する難治性Ewing肉腫 査読あり
山田 愛, 齋藤 祐介, 木下 真理子, 上村 幸代, 横山 亮平, 澤 大介, 盛武 浩
日本小児血液・がん学会雑誌 58 ( 1 ) 40 - 44 2021年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本小児血液・がん学会
Ewing肉腫（ES）は骨または軟部組織から発生する悪性腫瘍で，小児や若年成人に好発する．限局例では70%の無病生存が期待できるが，転移例や標準的化学療法抵抗例の予後は極めて不良である．症例は19歳男性．右腸骨腫瘍の生検組織より<i>EWSR1-FLI1</i>融合遺伝子を検出し，ESと診断した．胸部CTで多発肺転移を認め，ビンクリスチン，ドキソルビシン，シクロフォスファミド，イフォスファミド，エトポシドを用いたVDC/IE療法，原発部への放射線照射，ブスルファンとメルファランによる自家末梢血幹細胞移植併用大量化学療法，さらに複数の化学療法を施行するも非寛解であった．その後，パゾパニブ内服を開始し縮小効果を認め，7か月間の延命が可能であった．パゾパニブは経口薬のため在宅管理が可能で，さらに近年では長期生存例の報告も散見され，難治性ESの治療において考慮すべき薬剤と思われる．
DOI： 10.11412/jspho.58.40
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Hasegawa D., Tawa A., Tomizawa D., Watanabe T., Saito A.M., Kudo K., Taga T., Iwamoto S., Shimada A., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Koh K., Goto H., Kosaka Y., Miyachi H., Horibe K., Nakahata T., Adachi S.
Pediatric Blood and Cancer 67 ( 12 ) e28692 2020年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pediatric Blood and Cancer
We previously reported that risk-stratified therapy and intensive postremission chemotherapy (PRC) contributed to the improved survival of childhood acute myeloid leukemia (AML) in the AML99 study, which led us to consider a reduction in the number of PRC courses with more restrictive indications for stem cell transplantation (SCT) in the successor AML-05 study. We here report the outcome of AML patients without core-binding factor mutation (non-CBF AML) in the AML-05 study. Two-hundred eighty-nine children (age < 18 years old) with non-CBF AML were eligible. Patients with unfavorable cytogenetics and/or poor bone marrow response to the first induction course were candidates for SCT in the AML-05 study. After two courses of induction, a further three courses of PRC were given in AML-05, while four courses were given in the AML99 study. The 3-year event-free survival (EFS) rate in the AML-05 study (46.7%, 95% CI: 40.6-52.6%) was comparable to that of non-CBF AML in the AML99 study (51.5%, 95% CI: 42.7-59.6%) (P =.16). However, the 3-year overall survival (OS) rate in the AML-05 study (62.9%, 95% CI: 56.3-68.8%) was slightly lower than that in the AML99 study (71.6%, 95% CI: 63.2-78.5%) (P =.060), mainly due to decreased remission induction rate and increased nonrelapsed mortality. In conclusion, reductions in the number of PRC courses from four to three, together with repetitive cycles of high-dose cytarabine, were acceptable for non-CBF childhood AML.
DOI： 10.1002/pbc.28692
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Prevention of cisplatin-induced hearing-loss by sodium thiosulfate in medulloblastoma 査読あり
Harao T, Yamada A, Kinoshita M, Kamimura S, Moritake H
Pediatr Int 62 ( 10 ) 1204 - 1206 2020年9月
担当区分：筆頭著者, 最終著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1111/ped.14271
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Temozolomide and etoposide combination for the treatment of relapsed osteosarcoma 査読あり
Akazawa R., Umeda K., Saida S., Kato I., Hiramatsu H., Sakamoto A., Arakawa Y., Sumiyoshi S., Okamoto T., Moritake H., Adachi S., Takita J.
Japanese Journal of Clinical Oncology 50 ( 8 ) 948 - 952 2020年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Clinical Oncology
The prognosis of patients with relapsed osteosarcoma is extremely poor and the optimal treatment remains to be identified. Here, we retrospectively analysed the clinical outcomes of nine patients with relapsed osteosarcoma treated with temozolomide/etoposide. Of the two patients who received temozolomide/etoposide as palliative therapy for unresectable tumours, one remained alive with stable disease for >4 years. The remaining seven patients received temozolomide/etoposide as adjuvant therapy following resection of relapsed metastatic disease; of these, one was free from disease for 41 months. Potentially beneficial effects were observed in two of three O6-methylguanine-DNA methyltransferase protein-negative patients, whereas all five O6-methylguanine-DNA methyltransferase-positive patients experienced subsequent relapse. None of the patients experienced severe adverse effects requiring hospitalization. Temozolomide/etoposide is a feasible candidate as salvage therapy for relapsed osteosarcoma. Further studies are needed to verify the utility of O6-methylguanine-DNA methyltransferase protein expression as a biomarker for predicting the response to this treatment.
DOI： 10.1093/jjco/hyaa070
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Terui K., Toki T., Taga T., Iwamoto S., Miyamura T., Hasegawa D., Moritake H., Hama A., Nakashima K., Kanezaki R., Kudo K., Saito A.M., Horibe K., Adachi S., Tomizawa D., Ito E.
Genes Chromosomes and Cancer 59 ( 3 ) 160 - 167 2020年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Genes Chromosomes and Cancer
Myeloid leukemia associated with Down syndrome (ML-DS) is characterized by a predominance of acute megakaryoblastic leukemia, the presence of GATA1 mutations and a favorable outcome. Because DS children can also develop conventional acute myeloid leukemia with unfavorable outcome, detection of GATA1 mutations is important for diagnosis of ML-DS. However, myelofibrosis and the significant frequency of dry taps have hampered practical screening of GATA1 mutations using bone marrow (BM) samples. In response to those problems, 82 patients were enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-D11 study. GATA1 mutations were analyzed by Sanger sequencing (SS) using genomic DNA (gDNA) from BM and cDNA from peripheral blood (PB) followed by targeted next-generation sequencing (NGS) using pooled diagnostic samples. BM and PB samples were obtained from 71 (87%) and 82 (100%) patients, respectively. GATA1 mutations were detected in 46 (56%) and 58 (71%) patients by SS using BM gDNA and PB cDNA, respectively. Collectively, GATA1 mutations were identified in 73/82 (89%) patients by SS. Targeted NGS detected GATA1 mutations in 74/82 (90%) patients. Finally, combining the results of SS with those of targeted NGS, GATA1 mutations were identified in 80/82 (98%) patients. These results indicate that SS using BM gDNA and PB cDNA is a rapid and useful method for screening for GATA1 mutations in ML-DS patients. Thus, a combination of SS and targeted NGS is a sensitive and useful method to evaluate the actual incidence and clinical significance of GATA1 mutations in ML-DS patients.
DOI： 10.1002/gcc.22816
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日本における小児急性骨髄性白血病治療の歴史と現状，そして克服すべき課題について 査読あり
盛武 浩
日本小児血液・がん学会雑誌 57 ( 3 ) 240 - 250 2020年
担当区分：筆頭著者, 責任著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本小児血液・がん学会
小児白血病における急性骨髄性白血病（AML）の頻度は約25%とされ，日本では毎年約180例が新規に診断される．そして急性前骨髄球性白血病（APL），ダウン症関連骨髄性白血病（ML-DS），これら以外に分けて治療を行う．APLは抗がん剤にレチノイン酸を併用することにより安全な治療が可能となったが，三酸化ヒ素，ゲムツズマブ・オゾガマイシンの導入により晩期合併症の回避に加えてさらなる治療成績向上が期待できる．ML-DSは毒性を考慮し強度を弱めた化学療法により一定の治療成績は担保されるが，再発難治例の予後は著しく不良で初発治療の最適化が求められる．そこで，フローサイトメトリーとGATA1遺伝子変異を利用した微小残存病変検出による層別化が最適化に繋がることが期待されている．上記2つを除いたAMLは，染色体・遺伝子解析結果および初期治療反応性に基づくリスク分類により3群の層別化治療を行うが，再発難治例の予後改善が大きな問題である．さらなる成績向上のためには既存薬剤による治療では限界があり，近年成人に保険適用となったFLT3阻害薬をはじめとする新規薬剤の導入が必須である．
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Moritake H
[Rinsho ketsueki] The Japanese journal of clinical hematology 61 ( 6 ) 665 - 672 2020年
担当区分：筆頭著者, 責任著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本血液学会
小児白血病における急性骨髄性白血病（acute myeloid leukemia, AML）の頻度は約25％とされる。日本では，毎年約150例が新規に診断されるが，そのうち10％は初回寛解導入不能例となり，また一旦寛解が得られても30％が再発例となるため，さらなる治療成績向上のために新規薬剤の導入が強く望まれる。AMLは造血前駆細胞に様々な遺伝学的変化をきたして発症するヘテロな疾患である。近年の発症機序に関する研究の進歩によりAMLは遺伝学的タイプ別に分類されるようになってきた。その結果，特異的かつ効果的な治療を提供できる可能性が出てきた。今回の総説ではチロシンキナーゼ阻害薬，モノクローナル抗体，二重特異性抗体，キメラ抗原受容体T細胞療法，白血病代謝に関与する薬剤など，先行している成人での治療成績を紹介しながら，一部臨床応用前段階研究も含んだ形式で小児AMLに行われている臨床研究を紹介したい。
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急速に片側腎の機能低下を認めたシスチン尿症の1例 査読あり
黒木 純，此元 隆雄, 今村 秀明，中原 梢, 寺田 直樹, 上村 敏雄，賀本 敏行，盛武 浩
日本小児腎不全学会雑誌 40 297 - 300 2020年
担当区分：筆頭著者, 最終著者 記述言語：日本語 掲載種別：研究論文（学術雑誌）
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乳幼児早期に経後腹膜到達法による腹腔鏡下腎摘出を行った片側多嚢胞性異形成腎の１例 査読あり
長友 美佳, 此元 隆雄, 黒木 純, 今村 秀明, 中原 梢, 寺田 直樹, 上村 敏雄, 賀本 敏行, 盛武 浩
日本小児腎不全学会雑誌 40 301 - 304 2020年
担当区分：筆頭著者, 最終著者 記述言語：日本語 掲載種別：症例報告
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乳児期早期に腎摘出を行った多嚢胞性異形成腎の1例 査読あり
長友 美佳, 黒木 純, 今村 秀明, 此元 隆雄, 盛 武浩, 中原 梢, 寺田 直樹, 上村 敏雄, 賀本 敏行
日本小児腎臓病学会雑誌 32 ( 2 ) 157 - 158 2019年11月
掲載種別：症例報告
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Saito Y, Sawa D, Kinoshita M, Yamada A, Kamimura S, Suekane A, Ogoh H, Matsuo H, Adachi S, Taga T, Tomizawa D, Osato M, Soga T, Morishita K, Moritake H
Haematologica 105 ( 8 ) 2118 - 2129 2019年10月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Haematologica
Metabolic reprogramming of leukemia cells is important for survival, proliferation, and drug resistance under conditions of metabolic stress in the bone marrow. Deregulation of cellular metabolism, leading to development of leukemia, occurs through abnormally high expression of transcription factors such as MYC and Ecotropic Virus Integration site 1 protein homolog (EVI1). Overexpression of EVI1 in adults and children with mixed lineage leukemia-rearrangement acute myeloid leukemia (MLL-r AML) has a very poor prognosis. To identify a metabolic inhibitor for EVI1-induced metabolic reprogramming in MLL-r AML, we used an XFp extracellular flux analyzer to examine metabolic changes during leukemia development in mouse models of AML expressing MLL-AF9 and Evi1 (Evi1/MF9). Oxidative phosphorylation (OXPHOS) in Evi1/MF9 AML cells accelerated prior to activation of glycolysis, with a higher dependency on glutamine as an energy source. Furthermore, EVI1 played a role in glycolysis as well as driving production of metabolites in the tricarboxylic acid cycle. L-asparaginase (L-asp) exacerbated growth inhibition induced by glutamine starvation and suppressed OXPHOS and proliferation of Evi1/MF9 both in vitro and in vivo; high sensitivity to L-asp was caused by low expression of asparagine synthetase (ASNS) and L-asp-induced suppression of glutamine metabolism. In addition, samples from patients with EVI1+MF9 showed low ASNS expression, suggesting that it is a sensitive marker of L-asp treatment. Clarification of metabolic reprogramming in EVI1+ leukemia cells may aid development of treatments for EVI1+MF9 refractory leukemia.