Ph-positive Acute Lymphocytic Leukemia in a Man with Klinefelter Syndrome

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<ul><li><p> 0165-4608/00/$see front matterPII S0165-4608(99)00154-5</p><p>Cancer Genet Cytogenet 118:8384 (2000)</p><p> Elsevier Science Inc., 2000. All rights reserved.655 Avenue of the Americas, New York, NY 10010</p><p>LETTERS TO THE EDITOR</p><p>Ph-positive Acute Lymphocytic Leukemia in a Man with </p><p>Klinefelter Syndrome</p><p>Klinefelter syndrome (KS) is usually characterized by eu-nuchoidism, gynecomastia, small testes, infertility, ele-vated gonadotropins, mental retardation, and constitu-tional extra X chromosome. We describe here a case ofPhiladelphia (Ph) chromosome positive acute lympho-cytic leukemia in KS.</p><p>A 49-year-old Japanese male complaining of fevergreater than 38</p><p>8</p><p>C and fatigue was admitted to our hospitalin December 1997. He was a man of average intelligence,with a moderate physique. He manifested neither lym-phadenopathy nor hepatosplenomegaly. Hematologicaldata on admission were: platelet count 157 </p><p>3</p><p> 10</p><p>9</p><p>/l, whitecell count 15.4 </p><p>3</p><p> 10</p><p>9</p><p>/l with 43% blasts, and hemoglobinconcentration 14.4g/dl. Bone marrow (BM) aspirate fromthe sternum contained 77.6% lymphoblasts. Cytochemis-try studies showed negative reaction with peroxidase,with occasional blasts staining positive with acid phos-phatase. The BM contained an abnormal clonal karyotypeof 47,XXY with a complex translocation between the longarm of chromosome 9, the long arm of chromosome 22,and the long arm of chromosome 11, which was inter-preted as 47,XXY,t(9;22;11)(q34;q11.2;q13) (Table 1). Re-verse transcriptase polymerase chain reaction (RT-PCR)studies of BM mononuclear cells showed a major bcr/ablchimeric mRNA. His last blood picture, examined duringannual checkup six months prior to admission, was nor-mal. He was diagnosed as having a Ph chromosome posi-tive acute lymphocytic leukemia (ALL, L2).</p><p>After remission induction chemotherapy, the leukemiaresolved completely. Chromosomal analysis of BM cellsat remission revealed disappearance of the Ph chromo-some. Mosaicism XY/XXY and a nonclonal karyotype 47,XXY with additional material on the short arm of chromo-some 2 were noted (Table 1). The constitutional karyo-types of the peripheral blood cells stimulated with phyto-hemagglutinin showed mosaicism: XXY/XY with 66%XXY karyotype. After the second consolidation therapy,his BM contained a nonclonal karyotype of 47,XXY, withdeletion of chromosome 16 and the addition of a markerchromosome (Table 1). He is alive and free from the dis-ease 10 months after receiving an allogeneic bone marrowtransplantation.</p><p>This is, to our knowledge, the first case of Ph positiveALL associated with a 47,XXY karyotype; chronic myeloidleukemia (CML) has previously been described inKlinefelter syndrome patients [13]. Chromosomal analy-</p><p>sis on admission clearly indicated that the leukemia de-veloped in the XXY cells but not in the XY cells. A Phchromosome has been reported to occur in either XY orXXY cells, or both, in previous CML cases [13]. Whichclone is more susceptible to Ph chromosome developmentis unknown, though the transitional chromosome ab-normality found in his 47,XXY cells after remission makesit tempting to postulate that mitotic instability of the XXYcells may allow these cells to suffer malignant trans-formation.</p><p>The possible association between KS and the risk of de-veloping malignant diseases, especially nonseminomatousgerm cell tumors [4], have been mentioned. Hematologicmalignancies including acute myeloid leukemia [5],chronic lymphocytic leukemia [6], and ALL [7] have beenreported in association with KS. However, the question ofwhether or not men with KS are at risk of developing leu-kemia is a controversial one. A recent report analyzing 696men with KS [4] indicates no greater risk of developingleukemia as compared to the general population. Onlyroutine karyotyping of all new patients with leukemia mayclarify this issue, because men with mosaicism XY/XXYfrequently lack features of KS and are diagnosed bychance, as in this particular case.</p><p>TOMOFUMI YANO Department of MedicineSHOTA YUZURIO Okayama Rosai HospitalKAZUHI KIMURA Okayama, JapanTAKUMI KISHIMOTO</p><p>REFERENCES</p><p>1. Tough IM, Court Brown WH, Baikie AG, Buckton KE,Harnden DS, Jacobs PA, Williams JA (1961): Cytogenetic stud-ies in chronic myeloid leukemia and acute leukemia associ-ated with mongolism. Lancet 1:411417.</p><p>2. Fitzgerald PH, Pickering AF, Eiby JR (1971): Clonal origin of thePhiladelphia chromosome and chronic leukaemia. Evidencefrom a sex chromosome mosaic. Br J Haematol 21:473480.</p><p>3. Oguma N, Takemoto M, Oda K, Tanaka K, Shigeta C, SakataniK, Kanda N, Kuramoto A (1989): Chromic myelogeneous leu-kemia and Klinefelters syndrome. Eur J Haematol 42:207208.</p><p>4. Hasle H, Mellemgaard A, Nielsen J, Hansen J (1995): Cancerincidence in men with Klinefelter syndrome. Br J Cancer71:416420.</p><p>5. Mamunes P, Lapidus PH, Abbott JA, Roath S. (1961) Acuteleukaemia and Klinefelters syndrome. Lancet II:2627.</p></li><li><p> 84 </p><p>T. Yano et al.</p><p>6. Pienkos EJ, Meisner LF (1991): Adenocarcinoma of the pros-tate in a 41-year-old man with XXY karyotype and chroniclymphocytic leukemia: a report of a case. J Urol 145:148150.</p><p>7. Shaw MP, Eden OB, Grace E, Ellis PM (1992): Acute lympho-blastic leukemia and Klinefelters syndrome. Pediatr HematolOncol 9:8185.</p><p>Table 1</p><p>Results of cytogenetic study</p><p>KaryotypeNumber of cellsanalyzed</p><p>On admission 47,XXY,t(9;22;11)(q34;q11;q13)</p><p>10</p><p>46,XY 647,XXY 4</p><p>After induction Tx 46,XY 1047,XXY 947,XXY,add(2)</p><p>(p23)1</p><p>After 2nd consolidation Tx 47,XXY 1947,XXY,</p><p>2</p><p>16,</p><p>1</p><p>mar1</p><p>All cells were examined by G-banding technique.</p><p>Abbreviation</p><p>: Tx, therapy.</p></li></ul>


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