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Erschienen in: International Journal of Hematology 3/2023

06.04.2023 | Case Report

l-asparaginase as an efficient salvage therapy for refractory acute myeloid leukemia with chromosome 7 abnormalities: a case series

verfasst von: Kazuhiro Noguchi, Yasuhiro Ikawa, Mika Takenaka, Yuta Sakai, Toshihiro Fujiki, Rie Kuroda, Hideaki Maeba, Hiroaki Goto, Toshiyuki Kitoh, Taizo Wada

Erschienen in: International Journal of Hematology | Ausgabe 3/2023

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Abstract

Acute myeloid leukemia (AML) with chromosome 7 abnormalities has a dismal prognosis due to a poor complete remission (CR) rate after induction chemotherapy. Although various salvage therapies for refractory AML have been developed for adults, few salvage therapies are available for children. Here, we report the cases of three patients with refractory AML with chromosome 7 abnormalities (Patient 1, with inv(3)(q21;3q26.2) and monosomy 7; Patient 2, with der(7)t(1;7)(?;q22); patient 3, with monosomy 7) who were successfully treated with l-asparaginase (L-ASP) as salvage therapy. All three patients achieved CR several weeks after L-ASP treatment, and two patients successfully underwent hematopoietic stem cell transplantation (HSCT). Patient 2 relapsed after the second HSCT in the form of an intracranial lesion, but achieved and sustained CR for 3 years with weekly L-ASP maintenance therapy. Immunohistochemical staining for asparagine synthetase (ASNS), whose gene is located at 7q21.3, was performed for each patient. The result was negative in all patients, which suggests that haploid 7q21.3 and other chromosome 7 abnormalities leading to haploinsufficiency of ASNS contribute to a high susceptibility to L-ASP. In conclusion, L-ASP is a promising salvage therapy for refractory AML with chromosome 7 abnormalities, which are associated with ASNS haploinsufficiency.
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Literatur
1.
Zurück zum Zitat Kalwinsky DK, Raimondi SC, Schell MJ, Mirro J Jr, Santana VM, Behm F, et al. Prognostic importance of cytogenetic subgroups in de novo pediatric acute nonlymphocytic leukemia. J Clin Oncol. 1990;8:75–83.CrossRefPubMed Kalwinsky DK, Raimondi SC, Schell MJ, Mirro J Jr, Santana VM, Behm F, et al. Prognostic importance of cytogenetic subgroups in de novo pediatric acute nonlymphocytic leukemia. J Clin Oncol. 1990;8:75–83.CrossRefPubMed
2.
Zurück zum Zitat Hasle H, Alonzo TA, Auvrignon A, Behar C, Chang M, Creutzig U, et al. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood. 2007;109:4641–7.CrossRefPubMed Hasle H, Alonzo TA, Auvrignon A, Behar C, Chang M, Creutzig U, et al. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood. 2007;109:4641–7.CrossRefPubMed
3.
Zurück zum Zitat Martin ST, Daniel AP, Jessica KA, Frederick RA, Vijaya RB, Dale B, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Acute Myeloid Leukemia. Version 3.2021. Martin ST, Daniel AP, Jessica KA, Frederick RA, Vijaya RB, Dale B, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Acute Myeloid Leukemia. Version 3.2021.
4.
Zurück zum Zitat Hill JM, Roberts J, Loeb E, Khan A, MacLellan A, Hill RW. l-asparaginase therapy for leukemia and other malignant neoplasms. Remission in human leukemia. JAMA. 1967;202:882–8.CrossRefPubMed Hill JM, Roberts J, Loeb E, Khan A, MacLellan A, Hill RW. l-asparaginase therapy for leukemia and other malignant neoplasms. Remission in human leukemia. JAMA. 1967;202:882–8.CrossRefPubMed
5.
Zurück zum Zitat Heng HH, Shi XM, Scherer SW, Andrulis IL, Tsui LC. Refined localization of the asparagine synthetase gene (ASNS) to chromosome 7, region q21.3, and characterization of the somatic cell hybrid line 4AF/106/KO15. Cytogenet Cell Genet. 1994;66:135–8.CrossRefPubMed Heng HH, Shi XM, Scherer SW, Andrulis IL, Tsui LC. Refined localization of the asparagine synthetase gene (ASNS) to chromosome 7, region q21.3, and characterization of the somatic cell hybrid line 4AF/106/KO15. Cytogenet Cell Genet. 1994;66:135–8.CrossRefPubMed
6.
Zurück zum Zitat Sheng S, Moraga DA, Van Heeke G, Schuster SM. High-level expression of human asparagine synthetase and production of monoclonal antibodies for enzyme purification. Protein Expr Purif. 1992;3:337–46.CrossRefPubMed Sheng S, Moraga DA, Van Heeke G, Schuster SM. High-level expression of human asparagine synthetase and production of monoclonal antibodies for enzyme purification. Protein Expr Purif. 1992;3:337–46.CrossRefPubMed
7.
Zurück zum Zitat Kusano-Arai O, Iwanari H, Mochizuki Y, Nakata H, Kodama T, Kitoh T, Hamakubo T. Evaluation of the asparagine synthetase level in leukemia cells by monoclonal antibodies. Hybridoma (Larchmt). 2012;31(5):325–32.CrossRefPubMed Kusano-Arai O, Iwanari H, Mochizuki Y, Nakata H, Kodama T, Kitoh T, Hamakubo T. Evaluation of the asparagine synthetase level in leukemia cells by monoclonal antibodies. Hybridoma (Larchmt). 2012;31(5):325–32.CrossRefPubMed
8.
Zurück zum Zitat Yokosuka T, Ito M, Yoshino Y, Hirose A, Nakamura W, Sakurai Y, et al. Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis. Br J Haematol. 2022;196:764–8.CrossRefPubMed Yokosuka T, Ito M, Yoshino Y, Hirose A, Nakamura W, Sakurai Y, et al. Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis. Br J Haematol. 2022;196:764–8.CrossRefPubMed
10.
Zurück zum Zitat Buaboonnam J, Cao X, Pauley JL, Pui CH, Ribeiro RC, Rubnitz JE, et al. Sequential administration of methotrexate and asparaginase in relapsed or refractory pediatric acute myeloid leukemia. Pediatr Blood Cancer. 2013;60:1161–4.CrossRefPubMedPubMedCentral Buaboonnam J, Cao X, Pauley JL, Pui CH, Ribeiro RC, Rubnitz JE, et al. Sequential administration of methotrexate and asparaginase in relapsed or refractory pediatric acute myeloid leukemia. Pediatr Blood Cancer. 2013;60:1161–4.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Chiu M, Taurino G, Bianchi MG, Kilberg MS, Bussolati O. Asparagine synthetase in cancer: beyond acute lymphoblastic leukemia. Front Oncol. 2020;9:1480.CrossRefPubMedPubMedCentral Chiu M, Taurino G, Bianchi MG, Kilberg MS, Bussolati O. Asparagine synthetase in cancer: beyond acute lymphoblastic leukemia. Front Oncol. 2020;9:1480.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Bertuccio SN, Serravalle S, Astolfi A, Lonetti A, Indio V, Leszl A, et al. Identification of a cytogenetic and molecular subgroup of acute myeloid leukemias showing sensitivity to l-Asparaginase. Oncotarget. 2017;8:109915–23.CrossRefPubMedPubMedCentral Bertuccio SN, Serravalle S, Astolfi A, Lonetti A, Indio V, Leszl A, et al. Identification of a cytogenetic and molecular subgroup of acute myeloid leukemias showing sensitivity to l-Asparaginase. Oncotarget. 2017;8:109915–23.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Okada S, Hongo T, Yamada S, Watanabe C, Fujii Y, Ohzeki T, et al. In vitro efficacy of l-asparaginase in childhood acute myeloid leukaemia. Br J Haematol. 2003;123:802–9.CrossRefPubMed Okada S, Hongo T, Yamada S, Watanabe C, Fujii Y, Ohzeki T, et al. In vitro efficacy of l-asparaginase in childhood acute myeloid leukaemia. Br J Haematol. 2003;123:802–9.CrossRefPubMed
14.
Zurück zum Zitat Dübbers A, Würthwein G, Müller HJ, Schulze-Westhoff P, Winkelhorst M, Kurzknabe E, et al. Asparagine synthetase activity in paediatric acute leukaemias: AML-M5 subtype shows lowest activity. Br J Haematol. 2000;109:427–9.CrossRefPubMed Dübbers A, Würthwein G, Müller HJ, Schulze-Westhoff P, Winkelhorst M, Kurzknabe E, et al. Asparagine synthetase activity in paediatric acute leukaemias: AML-M5 subtype shows lowest activity. Br J Haematol. 2000;109:427–9.CrossRefPubMed
15.
Zurück zum Zitat Saito Y, Sawa D, Kinoshita M, Yamada A, Kamimura S, Suekane A, et al. EVI1 triggers metabolic reprogramming associated with leukemogenesis and increases sensitivity to l-asparaginase. Haematologica. 2020;105:2118–29.CrossRefPubMedPubMedCentral Saito Y, Sawa D, Kinoshita M, Yamada A, Kamimura S, Suekane A, et al. EVI1 triggers metabolic reprogramming associated with leukemogenesis and increases sensitivity to l-asparaginase. Haematologica. 2020;105:2118–29.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Rogers HJ, Vardiman JW, Anastasi J, Raca G, Savage NM, Cherry AM, et al. Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study. Haematologica. 2014;99:821–9.CrossRefPubMedPubMedCentral Rogers HJ, Vardiman JW, Anastasi J, Raca G, Savage NM, Cherry AM, et al. Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study. Haematologica. 2014;99:821–9.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Sitges M, Boluda B, Garrido A, Morgades M, Granada I, Barragan E, et al. Acute myeloid leukemia with inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2): Study of 61 patients treated with intensive protocols. Eur J Haematol. 2020;105:138–47.CrossRefPubMed Sitges M, Boluda B, Garrido A, Morgades M, Granada I, Barragan E, et al. Acute myeloid leukemia with inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2): Study of 61 patients treated with intensive protocols. Eur J Haematol. 2020;105:138–47.CrossRefPubMed
18.
Zurück zum Zitat Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Exp Hematol. 2014;42:247–51.CrossRefPubMed Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Exp Hematol. 2014;42:247–51.CrossRefPubMed
20.
Zurück zum Zitat Fathi AT, Wander SA, Faramand R, Emadi A. Biochemical, epigenetic, and metabolic approaches to target IDH mutations in acute myeloid leukemia. Semin Hematol. 2015;52:165–71.CrossRefPubMed Fathi AT, Wander SA, Faramand R, Emadi A. Biochemical, epigenetic, and metabolic approaches to target IDH mutations in acute myeloid leukemia. Semin Hematol. 2015;52:165–71.CrossRefPubMed
Metadaten
Titel
l-asparaginase as an efficient salvage therapy for refractory acute myeloid leukemia with chromosome 7 abnormalities: a case series
verfasst von
Kazuhiro Noguchi
Yasuhiro Ikawa
Mika Takenaka
Yuta Sakai
Toshihiro Fujiki
Rie Kuroda
Hideaki Maeba
Hiroaki Goto
Toshiyuki Kitoh
Taizo Wada
Publikationsdatum
06.04.2023
Verlag
Springer Nature Singapore
Erschienen in
International Journal of Hematology / Ausgabe 3/2023
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-023-03591-1

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