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09.05.2024 | Original Article

Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients

verfasst von: Yu Shi, Xiao Chen, Huimin Jin, Liying Zhu, Ming Hong, Yu Zhu, Yujie Wu, Hairong Qiu, Yan Wang, Qian Sun, Hui Jin, Jianyong Li, Sixuan Qian, Chun Qiao

Erschienen in: Annals of Hematology

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Abstract

Background: Acute myeloid leukemia (AML) patients with various nucleophosmin 1 (NPM1) mutations are controversial in the prognosis. This study aimed to investigate the prognosis of patients according to types of NPM1 mutations (NPM1^mut). Methods: Bone marrow samples of 528 patients newly diagnosed with AML, were collected for morphology, immunology, cytogenetics, and molecular biology examinations. Gene mutations were detected by next-generation sequencing (NGS) technology. Results: About 25.2% of cases exhibited NPM1^mut. 83.5% of cases were type A, while type B and D were respectively account for 2.3% and 3.0%. Furthermore, 15 cases of rare types were identified, of which 2 cases have not been reported. Clinical characteristics were similar between patients with A-type NPM1 mutations (NPM1^{A − type mut}) and non-A-type NPM1 mutations (NPM1^{non − A−type mut}). Event-free survival (EFS) was significantly different between patients with low NPM1^{non − A−type mut} variant allele frequency (VAF) and low NPM1^{A − type mut} VAF (median EFS = 3.9 vs. 8.5 months, P = 0.020). The median overall survival (OS) of the NPM1^{non − A−type mut}FLT3-ITD^mut group, the NPM1^{A − type mut}FLT3-ITD^mut group, the NPM1^{non − A−type mut}FLT3-ITD^wt group, and the NPM1^{A − type mut}FLT3-ITD^wt group were 3.9, 10.7, 17.3 and 18.8 months, while the median EFS of the corresponding groups was 1.4, 5.0, 7.6 and 9.2 months (P < 0.0001 and P = 0.004, respectively). Conclusions: No significant difference was observed in OS and EFS between patients with NPM1^{A − type mut} and NPM1^{non − A−type mut}. However, types of NPM1 mutations and the status of FLT3-ITD mutations may jointly have an impact on the prognosis of AML patients.

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De Kouchkovsky I, Abdul-Hay M (2016) Acute myeloid leukemia: a comprehensive review and 2016 update. Blood cancer J 6(7):e441. https://doi.org/10.1038/bcj.2016.50CrossRefPubMedPubMedCentral

Namratha Udupa MS, Babu KG, Suresh Babu MC, Lakshmaiah KC, Lokanatha D, Jacob AL, Lokesh KN, Rajeev LK, Rudresh AH, Devi L (2020) Clinical profile, cytogenetics and treatment outcomes of adult acute myeloid leukemia. J Cancer Res Ther 16(1):18–22. https://doi.org/10.4103/jcrt.JCRT_1162_16CrossRefPubMed

Nakajima H (2019) [Genetic abnormalities in AML]. [Rinsho Ketsueki] Japanese J Clin Hematol 60(6):584–593. https://doi.org/10.11406/rinketsu.60.584CrossRef

Yang JJ, Park TS, Wan TS (2017) Recurrent cytogenetic abnormalities in Acute myeloid leukemia. Methods Mol Biol 1541:223–245. https://doi.org/10.1007/978-1-4939-6703-2_19CrossRefPubMed

Zhu YM, Wang PP, Huang JY, Chen YS, Chen B, Dai YJ, Yan H, Hu Y, Cheng WY, Ma TT, Chen SJ, Shen Y (2017) Gene mutational pattern and expression level in 560 acute myeloid leukemia patients and their clinical relevance. J Translational Med 15(1):178. https://doi.org/10.1186/s12967-017-1279-4CrossRef

Chen X, Zhu H, Qiao C, Zhao S, Liu L, Wang Y, Jin H, Qian S, Wu Y (2021) Next-generation sequencing reveals gene mutations landscape and clonal evolution in patients with acute myeloid leukemia. Hematology 26(1):111–122. https://doi.org/10.1080/16078454.2020.1858610CrossRefPubMed

Kihara R, Nagata Y, Kiyoi H, Kato T, Yamamoto E, Suzuki K, Chen F, Asou N, Ohtake S, Miyawaki S, Miyazaki Y, Sakura T, Ozawa Y, Usui N, Kanamori H, Kiguchi T, Imai K, Uike N, Kimura F, Kitamura K, Nakaseko C, Onizuka M, Takeshita A, Ishida F, Suzushima H, Kato Y, Miwa H, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Naoe T (2014) Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia 28(8):1586–1595. https://doi.org/10.1038/leu.2014.55CrossRefPubMed

Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, Appelbaum FR (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96(13):4075–4083CrossRefPubMed

Schneider F, Hoster E, Unterhalt M, Schneider S, Dufour A, Benthaus T, Mellert G, Zellmeier E, Kakadia PM, Bohlander SK, Feuring-Buske M, Buske C, Braess J, Heinecke A, Sauerland MC, Berdel WE, Buchner T, Wormann BJ, Hiddemann W, Spiekermann K (2012) The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype. Blood 119(19):4383–4386. https://doi.org/10.1182/blood-2010-12-327072CrossRefPubMed

10.

Hurtado R, Guirales F, Tirado CA (2021) ASXL1 gene in AML. J Association Genetic Technol 47(2):60–68

11.

Libura M, Bialopiotrowicz E, Giebel S, Wierzbowska A, Roboz GJ, Piatkowska-Jakubas B, Pawelczyk M, Gorniak P, Borg K, Wojtas M, Florek I, Matiakowska K, Jazwiec B, Solarska I, Noyszewska-Kania M, Piechna K, Zawada M, Czekalska S, Salamanczuk Z, Karabin K, Wasilewska K, Paluszewska M, Urbanowska E, Gajkowska-Kulik J, Semenczuk G, Rybka J, Wrobel T, Ejduk A, Kata D, Grosicki S, Robak T, Pluta A, Kominek A, Piwocka K, Pyziak K, Sroka-Porada A, Wrobel A, Przybylowicz A, Wojtaszewska M, Lewandowski K, Gil L, Piekarska A, Knopinska W, Bolkun L, Warzocha K, Kuliczkowski K, Sacha T, Basak G, Jedrzejczak WW, Holowiecki J, Juszczynski P, Haus O (2021) IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen. Sci Rep 11(1):10017. https://doi.org/10.1038/s41598-021-88120-yCrossRefPubMedPubMedCentral

12.

Dunlap JB, Leonard J, Rosenberg M, Cook R, Press R, Fan G, Raess PW, Druker BJ, Traer E (2019) The combination of NPM1, DNMT3A, and IDH1/2 mutations leads to inferior overall survival in AML. Am J Hematol 94(8):913–920. https://doi.org/10.1002/ajh.25517CrossRefPubMedPubMedCentral

13.

Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ (2010) Phase IIB trial of oral midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncology: Official J Am Soc Clin Oncol 28(28):4339–4345. https://doi.org/10.1200/JCO.2010.28.9678CrossRef

14.

Chi SG, Minami Y (2022) Emerging targeted therapy for specific genomic abnormalities in Acute myeloid leukemia. Int J Mol Sci 23(4). https://doi.org/10.3390/ijms23042362

15.

Döhner H, Weber D, Krzykalla J, Fiedler W, Wulf G, Salih H, Lübbert M, Kühn MWM, Schroeder T, Salwender H, Götze K, Westermann J, Fransecky L, Mayer K, Hertenstein B, Ringhoffer M, Tischler HJ, Machherndl-Spandl S, Schrade A, Paschka P, Gaidzik VI, Theis F, Thol F, Heuser M, Schlenk RF, Bullinger L, Saadati M, Benner A, Larson R, Stone R, Döhner K, Ganser A (2022) Midostaurin plus intensive chemotherapy for younger and older patients with AML and FLT3 internal tandem duplications. Blood Adv 6(18):5345–5355. https://doi.org/10.1182/bloodadvances.2022007223CrossRefPubMedPubMedCentral

16.

Oñate G, Pratcorona M, Garrido A, Artigas-Baleri A, Bataller A, Tormo M, Arnan M, Vives S, Coll R, Salamero O, Vall-Llovera F, Sampol A, Garcia A, Cervera M, Avila SG, Bargay J, Ortín X, Nomdedéu JF, Esteve J, Sierra J, Spanish Cooperative Group for the Study and Treatment of Acute Leukemias and Myelodysplasias (CETLAM) (2023) Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort. Blood Cancer J 13(1):69. https://doi.org/10.1038/s41408-023-00839-1CrossRefPubMedPubMedCentral

17.

Shimony S, Canaani J, Kugler E, Nachmias B, Ram R, Henig I, Frisch A, Ganzel C, Vainstein V, Moshe Y, Aumann S, Yeshurun M, Ofran Y, Raanani P, Wolach O (2022) Gilteritinib monotherapy for relapsed/refractory FLT3 mutated acute myeloid leukemia: a real-world, multi-center, matched analysis. Ann Hematol 101(9):2001–2010. https://doi.org/10.1007/s00277-022-04895-8CrossRefPubMed

18.

Chen N, Pan J, Zhou Y, Mao L, Lou Y, Qian J, Xu G, Wei J, Zhou D, Shou L, Huang L, Yan M, Zeng H, Fan C, Wu G, Feng W, Tong H, Jin J, Wang H (2023) Gilteritinib-based combination therapy in adult relapsed/refractory FLT3-mutated acute myeloid leukaemia. Br J Haematol. https://doi.org/10.1111/bjh.19182CrossRefPubMedPubMedCentral

19.

Birendra KC, DiNardo CD (2016) Evidence for clinical differentiation and differentiation syndrome in patients with Acute myeloid leukemia and IDH1 mutations treated with the targeted mutant IDH1 inhibitor, AG-120. Clinical lymphoma, myeloma & leukemia 16. 8460–465. https://doi.org/10.1016/j.clml.2016.04.006

20.

Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, Kantarjian HM, Collins R, Patel MR, Frankel AE, Stein A, Sekeres MA, Swords RT, Medeiros BC, Willekens C, Vyas P, Tosolini A, Xu Q, Knight RD, Yen KE, Agresta S, de Botton S, Tallman MS (2017) Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 130(6):722–731. https://doi.org/10.1182/blood-2017-04-779405CrossRefPubMedPubMedCentral

21.

Leong SM, Tan BX, Bte Ahmad B, Yan T, Chee LY, Ang ST, Tay KG, Koh LP, Yeoh AE, Koay ES, Mok YK, Lim TM (2010) Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and – 8 inhibition. Blood 116(17):3286–3296. https://doi.org/10.1182/blood-2009-12-256149CrossRefPubMed

22.

Hindley A, Catherwood MA, McMullin MF, Mills KI (2021) Significance of NPM1 gene mutations in AML. Int J Mol Sci 22(18). https://doi.org/10.3390/ijms221810040

23.

Li Z, Boone D, Hann SR (2008) Nucleophosmin interacts directly with c-Myc and controls c-Myc-induced hyperproliferation and transformation. Proc Natl Acad Sci USA 105(48):18794–18799. https://doi.org/10.1073/pnas.0806879105CrossRefPubMedPubMedCentral

24.

Colombo E, Alcalay M, Pelicci PG (2011) Nucleophosmin and its complex network: a possible therapeutic target in hematological diseases. Oncogene 30(23):2595–2609. https://doi.org/10.1038/onc.2010.646CrossRefPubMed

25.

Federici L, Falini B (2013) Nucleophosmin mutations in acute myeloid leukemia: a tale of protein unfolding and mislocalization. Protein Science: Publication Protein Soc 22(5):545–556. https://doi.org/10.1002/pro.2240CrossRef

26.

Ahmad F, Mandava S, Das BR (2009) Mutations of NPM1 gene in de novo acute myeloid leukaemia: determination of incidence, distribution pattern and identification of two novel mutations in Indian population. Hematol Oncol 27(2):90–97. https://doi.org/10.1002/hon.883CrossRefPubMed

27.

Peng J, Fu B, Fu G, Zhao X, Li X, Chen F (2017) Effect of NPM1 type B mutation on the proliferation, invasion and chemosensitivity of THP-1 leukemia cells. Pharmazie 72(10):608–613. https://doi.org/10.1691/ph.2017.7473CrossRefPubMed

28.

Alarbeed IF, Wafa A, Moassass F, Al-Halabi B, Alachkar W, Aboukhamis I (2021) Two novel mutations of the NPM1 gene in Syrian adult patients with Acute myeloid leukemia and Normal Karyotype. Asian Pac J cancer Prevention: APJCP 22(1):227–232. https://doi.org/10.31557/APJCP.2021.22.1.227CrossRef

29.

Duployez N, Chebrek L, Helevaut N, Fournier E, Bemba M, Caillault A, Geffroy S, Preudhomme C (2018) A novel type of NPM1 mutation characterized by multiple internal tandem repeats in a case of cytogenetically normal acute myeloid leukemia. Haematologica 103(12):e575–e577. https://doi.org/10.3324/haematol.2018.190959CrossRefPubMedPubMedCentral

30.

Nagase R, Inoue D, Pastore A, Fujino T, Hou HA, Yamasaki N, Goyama S, Saika M, Kanai A, Sera Y, Horikawa S, Ota Y, Asada S, Hayashi Y, Kawabata KC, Takeda R, Tien HF, Honda H, Abdel-Wahab O, Kitamura T (2018) Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation. J Exp Med 215(6):1729–1747. https://doi.org/10.1084/jem.20171151CrossRefPubMedPubMedCentral

31.

Chan SM, Majeti R (2013) Role of DNMT3A, TET2, and IDH1/2 mutations in pre-leukemic stem cells in acute myeloid leukemia. Int J Hematol 98(6):648–657. https://doi.org/10.1007/s12185-013-1407-8CrossRefPubMedPubMedCentral

32.

Falini B, Brunetti L, Sportoletti P, Martelli MP (2020) NPM1-mutated acute myeloid leukemia: from bench to bedside. Blood 136(15):1707–1721. https://doi.org/10.1182/blood.2019004226CrossRefPubMed

33.

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405. https://doi.org/10.1182/blood-2016-03-643544CrossRefPubMed

34.

Yu J, Li Y, Zhang D, Wan D, Jiang Z (2020) Clinical implications of recurrent gene mutations in acute myeloid leukemia. Experimental Hematol Oncol 9:4. https://doi.org/10.1186/s40164-020-00161-7CrossRef

35.

Falini B (2010) Acute myeloid leukemia with mutated nucleophosmin (NPM1): molecular, pathological, and clinical features. Cancer Treat Res 145:149–168. https://doi.org/10.1007/978-0-387-69259-3_9CrossRefPubMed

36.

Dohner K, Thiede C, Jahn N, Panina E, Gambietz A, Larson RA, Prior TW, Marcucci G, Jones D, Krauter J, Heuser M, Voso MT, Ottone T, Nomdedeu JF, Mandrekar SJ, Klisovic RB, Wei AH, Sierra J, Sanz MA, Brandwein JM, de Witte T, Jansen JH, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Gathmann I, Benner A, Pallaud C, Stone RM, Dohner H, Bloomfield CD (2020) Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia. Blood 135(5):371–380. https://doi.org/10.1182/blood.2019002697CrossRefPubMedPubMedCentral

37.

Park BG, Chi HS, Park SJ, Min SK, Jang S, Park CJ, Kim DY, Lee JH, Lee JH, Lee KH (2012) Clinical implications of non-A-type NPM1 and FLT3 mutations in patients with normal karyotype acute myeloid leukemia. Acta Haematol 127(2):63–71. https://doi.org/10.1159/000331509CrossRefPubMed

38.

Pastore F, Greif PA, Schneider S, Ksienzyk B, Mellert G, Zellmeier E, Braess J, Sauerland CM, Heinecke A, Krug U, Berdel WE, Buechner T, Woermann B, Hiddemann W, Spiekermann K (2014) The NPM1 mutation type has no impact on survival in cytogenetically normal AML. PLoS ONE 9(10):e109759. https://doi.org/10.1371/journal.pone.0109759CrossRefPubMedPubMedCentral

39.

Koh Y, Park J, Bae EK, Ahn KS, Kim I, Bang SM, Lee JH, Yoon SS, Lee DS, Lee YY, Park S, Kim BK (2009) Non-A type nucleophosmin 1 gene mutation predicts poor clinical outcome in de novo adult acute myeloid leukemia: differential clinical importance of NPM1 mutation according to subtype. Int J Hematol 90(1):1–5. https://doi.org/10.1007/s12185-009-0350-1CrossRefPubMed

40.

Marcucci G, Mrozek K, Ruppert AS, Archer KJ, Pettenati MJ, Heerema NA, Carroll AJ, Koduru PR, Kolitz JE, Sterling LJ, Edwards CG, Anastasi J, Larson RA, Bloomfield CD (2004) Abnormal cytogenetics at date of morphologic complete remission predicts short overall and disease-free survival, and higher relapse rate in adult acute myeloid leukemia: results from cancer and leukemia group B study 8461. J Clin Oncology: Official J Am Soc Clin Oncol 22(12):2410–2418. https://doi.org/10.1200/JCO.2004.03.023CrossRef

41.

Saburi M, Ogata M, Satou T, Soga Y, Itani K, Kohno K, Kondo Y, Nakayama T (2020) Prognostic implications of TdT expression in acute myeloid leukemia with an intermediate-risk karyotype. Int J Hematol 112(1):17–23. https://doi.org/10.1007/s12185-020-02871-4CrossRefPubMed

42.

Patel SS, Kuo FC, Gibson CJ, Steensma DP, Soiffer RJ, Alyea EP 3rd, Chen YA, Fathi AT, Graubert TA, Brunner AM, Wadleigh M, Stone RM, DeAngelo DJ, Nardi V, Hasserjian RP, Weinberg OK (2018) High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML. Blood 131(25):2816–2825. https://doi.org/10.1182/blood-2018-01-828467CrossRefPubMedPubMedCentral

43.

Boddu PC, Kadia TM, Garcia-Manero G, Cortes J, Alfayez M, Borthakur G, Konopleva M, Jabbour EJ, Daver NG, DiNardo CD, Naqvi K, Yilmaz M, Short NJ, Pierce S, Kantarjian HM, Ravandi F (2019) Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes. Cancer 125(7):1091–1100. https://doi.org/10.1002/cncr.31885CrossRefPubMed

44.

Pollyea DA, Bixby D, Perl A, Bhatt VR, Altman JK, Appelbaum FR, de Lima M, Fathi AT, Foran JM, Gojo I, Hall AC, Jacoby M, Lancet J, Mannis G, Marcucci G, Martin MG, Mims A, Neff J, Nejati R, Olin R, Percival ME, Prebet T, Przespolewski A, Rao D, Ravandi-Kashani F, Shami PJ, Stone RM, Strickland SA, Sweet K, Vachhani P, Wieduwilt M, Gregory KM, Ogba N, Tallman MS (2021) NCCN guidelines insights: Acute Myeloid Leukemia, Version 2.2021. J Natl Compr Cancer Network: JNCCN 19(1):16–27. https://doi.org/10.6004/jnccn.2021.0002CrossRefPubMed

45.

Chou WC, Tang JL, Lin LI, Yao M, Tsay W, Chen CY, Wu SJ, Huang CF, Chiou RJ, Tseng MH, Lin DT, Lin KH, Chen YC, Tien HF (2006) Nucleophosmin mutations in de novo acute myeloid leukemia: the age-dependent incidences and the stability during disease evolution. Cancer Res 66(6):3310–3316. https://doi.org/10.1158/0008-5472.CAN-05-4316CrossRefPubMed

46.

Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O’Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Dohner K, Schlenk RF, Dohner H, Campbell PJ (2016) Genomic classification and prognosis in Acute myeloid leukemia. N Engl J Med 374(23):2209–2221. https://doi.org/10.1056/NEJMoa1516192CrossRefPubMedPubMedCentral

47.

Heath EM, Chan SM, Minden MD, Murphy T, Shlush LI, Schimmer AD (2017) Biological and clinical consequences of NPM1 mutations in AML. Leukemia 31(4):798–807. https://doi.org/10.1038/leu.2017.30CrossRefPubMed

48.

Fournier E, Heiblig M, Lespinasse C, Flandrin-Gresta P, Geay A, Miguet L, Fenwarth L, Vallat L, Soubeyrand B, Marceau-Renaut A, Plesa A, Preudhomme C, Sujobert P, Hayette S, Duployez N, Huet S (2022) Molecular heterogeneity and measurable residual disease of rare NPM1 mutations in acute myeloid leukemia: a nationwide experience from the GBMHM study group. Leukemia 36(5):1390–1400. https://doi.org/10.1038/s41375-022-01534-zCrossRefPubMed

49.

Wakita S, Yamaguchi H, Ueki T, Usuki K, Kurosawa S, Kobayashi Y, Kawata E, Tajika K, Gomi S, Koizumi M, Fujiwara Y, Yui S, Fukunaga K, Ryotokuji T, Hirakawa T, Arai K, Kitano T, Kosaka F, Tamai H, Nakayama K, Fukuda T, Inokuchi K (2016) Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia. Leukemia 30(3):545–554. https://doi.org/10.1038/leu.2015.288CrossRefPubMed

50.

Pasca S, Jurj A, Tomuleasa C, Zdrenghea M (2020) TET2/IDH1/2/WT1 and NPM1 mutations influence the RUNX1 expression correlations in Acute myeloid leukemia. Medicina 56(12). https://doi.org/10.3390/medicina56120637

51.

Tian X, Xu Y, Yin J, Tian H, Chen S, Wu D, Sun A (2014) TET2 gene mutation is unfavorable prognostic factor in cytogenetically normal acute myeloid leukemia patients with NPM1 + and FLT3-ITD - mutations. Int J Hematol 100(1):96–104. https://doi.org/10.1007/s12185-014-1595-xCrossRefPubMed

52.

Heiblig M, Sujobert P, Hayette S, Balsat M, Elhamri M, Salles G, Thomas X (2019) Impact of NPM1 mutation subtypes on treatment outcome in AML: the Lyon-University Hospital experience. Leuk Res 76:29–32. https://doi.org/10.1016/j.leukres.2018.11.016CrossRefPubMed

53.

Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM (2019) Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev 36:70–87. https://doi.org/10.1016/j.blre.2019.04.005CrossRefPubMed

54.

Abdallah M, Xie Z, Ready A, Manogna D, Mendler JH, Loh KP (2020) Management of Acute myeloid leukemia (AML) in older patients. Curr Oncol Rep 22(10):103. https://doi.org/10.1007/s11912-020-00964-1CrossRefPubMedPubMedCentral

Titel: Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients
verfasst von: Yu Shi
Xiao Chen
Huimin Jin
Liying Zhu
Ming Hong
Yu Zhu
Yujie Wu
Hairong Qiu
Yan Wang
Qian Sun
Hui Jin
Jianyong Li
Sixuan Qian
Chun Qiao
Publikationsdatum: 09.05.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-024-05786-w

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