We describe a patient with acute myeloid leukemia (AML) who had a normal karyotype at diagnosis and was negative for NPM1 and FLT3 mutations, but had a KIT G565V mutation in exon 11. This has not been described previously in AML. The patient received induction and consolidation chemotherapy and was in hematologic remission for 351 days when deletion 7q was cytogenetically detected in 8% of the bone marrow cells. After an initial treatment of azacitidine followed by decitabine, an unrelated trisomy 13 clone was identified, followed by subclonal rearrangement of ETV6. The patient underwent reinduction with high-dose cytarabine and mitoxantrone followed by voluntary-unrelated-donor allogeneic stem cell transplantation with a reduced-intensity conditioning. As of writing, the patient is in complete hematologic and cytogenetic remission with 100% donor cell engraftment.

Grimwade D, Mrozek K: Diagnostic and prognostic value of cytogenetics in acute myeloid leukemia. Hematol Oncol Clin N Am 2011;25:1135-1161.
Thiede C, Koch S, Creutzig E, Steudel C, Illmer T, Schaich M, Ehninger G: Prevalence and prognostic impact of NPM1 mutations in 1,485 adult patients with acute myeloid leukemia (AML). Blood 2006;107:4011-4020.
Frohling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis K, Dohner H, Dohner K: Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group ULM. Blood 2002;100:4372-4380.
Barjesteh van Waalwijk van Doorn-Khosrovani S, Erpelinck C, Meijer J, van Oosterhoud S, van Putten WL, Valk PJ, Berna Beverloo H, Tenen DG, Lowenberg B, Delwel R: Biallelic mutations in the CEBPA gene and low CEBPA expression levels as prognostic markers in intermediate-risk AML. Hematol J 2003;4:31-40.
Riera L, Marmont F, Toppino D, Frairia C, Sismondi F, Audisio E, Di Bello C, D'Ardia S, Di Celle PF, Messa E, Inghirami G, Vitolo U, Pich A: Core-binding factor acute myeloid leukaemia and c-KIT mutations. Oncol Rep 2013;29:1867-1872.
Care RS, Valk PJ, Goodeve AC, Abu-Duhier FM, Geertsma-Kleinekoort W, Wilson GA, Gari MA, Peake IR, Wenberg BL, Reilly JT: Incidence and prognosis of C-KIT and FLT3 mutations in core-binding factor (CBF) acute myeloid leukaemias. Br J Haematol 2003;121:775-777.
Paschka P, Marcucci G, Ruppert AS, Mrozek K, Chen H, Kittles RA, Vukosavljevic T, Perrotti D, Vardiman JW, Carroll AJ, Kolitz JE, Larson RA, Bloomfield CD: Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 2006;24:3904-3911.
Fenaux P, Gattermann N, Seymour JF, Hellstrom-Lindberg E, Mufti GJ, Duehrsen U, Gore SD, Ramos F, Beyne-Rauzy O, List A, Mckenzie D, Backstrom J, Beach CL: Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-c. Br J Haematol 2009;149:244-249.
Baer MR, Bloomfield CD: Trisomy 13 in acute leukemia. Leukemia and Lymphoma 1992;7:1-6.
Dohner H, Arthur DC, Ball ED, Sobol RE, Davey FR, Lawrence D, Gordon L, Patil SR, Surana RB, Testa JR, Verma RS, Schiffer CA, Wurster-Hill DH, Bloomfield CD: Trisomy 13:A new recurring chromosome abnormality in acute leukemia. Blood 1990;76:1614-1621.
Lasota J, Jasinski M, Sarlomo-Rikala M, Miettinen M: Mutations in exon 11 of c-KIT occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. AM J Pathol 1999;154:53-60.
Hussain SR, Siddiqui A, Vargas-Medrano J, Nagvi H, Mohl J, Mahdi F, Ahmad F: Identification of novel point mutations in c-KIT gene from leukemia cases: a study from Lucknow Uttar Pradesh, India. Tecnociencia Chihuahua 2012;6:22-32.
Corbacioglu S, Kilic M, Westhoff MA, Reinhardt D, Fulda S, Debatin KM: Newly identified c-KIT receptor tyrosine kinase ITD in childhood AML induces Ligand-independent growth and is responsive to a synergistic effect of imatinib and rapamycin.Blood 2006;108:3504-3513.
Koreth J, Schlenk R, Kopecky KJ: Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: Systemic review and Meta-analysis of prospective clinical trials. JAMA 2009;301:2349-2361.
Burnett AK, Goldstone A, Hills RK: Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission. J Clin Oncol 2013;31:1293-1301.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.