CASE REPORT Monosomies 7p and 12p and FLT3 internal tandem duplication: possible markers for diagnosis of T/myeloid biphenotypic acute leukemia and its clonal evolution Yosuke Matsumoto Æ Tomohiko Taki Æ Yoshiko Fujimoto Æ Kyoko Taniguchi Æ Daisuke Shimizu Æ Kazuho Shimura Æ Hitoji Uchiyama Æ Junya Kuroda Æ Kenichi Nomura Æ Tohru Inaba Æ Chihiro Shimazaki Æ Shigeo Horiike Æ Masafumi Taniwaki Received: 9 June 2008 / Revised: 26 January 2009 / Accepted: 4 February 2009 / Published online: 24 March 2009 Ó The Japanese Society of Hematology 2009 Abstract Biphenotypic acute leukemia co-expressing T-lymphoid and myeloid markers is rare, accounting for less than 1% of acute leukemias. However, several clinical characteristics including male predominance, frequent lymphadenopathy and unfavorable outcome have been identified. Recurrence of monosomies 7p and/or 12p in T/myeloid biphenotypic acute leukemia has been reported. We treated a patient with T/myeloid biphenotypic acute leukemia showing clonal chromosomal and genetic abnor- malities including dic(7;12)(p11;p11) and Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication. Cytogenetic analysis of both bone marrow and lymph node cells disclosed that the patient’s lymph node leukemia cells had chromo- somal abnormalities in addition to dic(7;12). Our findings suggest that the leukemia cells of systemic lymphadenopathy had evolved as secondary cells from marrow leukemia cells. The patient was successfully treated with induction chemo- therapy for acute myeloid leukemia followed by allogeneic bone marrow transplantation. Keywords Monosomies Á FLT3-ITD Á Biphenotypic acute leukemia Á Stem cell transplantation 1 Introduction In the French-American-British classification, acute leukemias are classified as lymphoid or myeloid lineage on the basis of myeloperoxidase (MPO) staining. In a minority of cases, however, blast cells simultaneously express markers for two or three lineages of myeloids and B- and T-lymphoids. According to the World Health Organization (WHO) classification of tumors [1], these cases are classified as biphenotypic acute leukemia, and a diagnostic scoring system for this previously ill-defined entity was proposed by the European group for the immunological classification of leukemias (EGIL) [2]. This system is based on the number and specificity of the lymphoid and myeloid markers expressed on blast cells. The most common immunophenotype of bipheno- typic acute leukemia (60–70%) consists of co-expressed B-lymphoid and myeloid markers, while co-expressed T-lymphoid and myeloid markers are less frequent (20–30%) [3–6]. Specific chromosomal and genetic abnormalities and definitive treatment have not yet been reported for T/myeloid biphenotypic acute leukemia. This report concerns a patient with T/myeloid bipheno- typic acute leukemia, featuring dic(7;12)(p11;p11) and Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (FLT3-ITD) in both marrow and lymph node cells, who was successfully treated with myeloablative stem cell transplantation. 2 Case report A 50-year-old man was admitted to our hospital because of anorexia in June 2004. Physical examination and computed tomography detected systemic lymphadenopathy involving Y. Matsumoto (&) Á Y. Fujimoto Á K. Taniguchi Á D. Shimizu Á K. Shimura Á H. Uchiyama Á J. Kuroda Á K. Nomura Á C. Shimazaki Á S. Horiike Á M. Taniwaki Department of Molecular Hematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan e-mail: yosuke-m@koto.kpu-m.ac.jp T. Taki Á D. Shimizu Á T. Inaba Á M. Taniwaki Department of Molecular Laboratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan 123 Int J Hematol (2009) 89:352–358 DOI 10.1007/s12185-009-0268-7