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Cancer Genet Cytogenet 118:83–84 (2000)
Elsevier Science Inc., 2000. All rights reserved.655 Avenue of the Americas, New York, NY 10010
LETTERS TO THE EDITOR
Ph-positive Acute Lymphocytic Leukemia in a Man with
Klinefelter Syndrome
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.
A 49-year-old Japanese male complaining of fevergreater than 38
8
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
3
10
9
/l, whitecell count 15.4
3
10
9
/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).
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.
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 [1–3]. Chromosomal analy-
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 [1–3]. 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.
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.
TOMOFUMI YANO Department of MedicineSHOTA YUZURIO Okayama Rosai HospitalKAZUHI KIMURA Okayama, JapanTAKUMI KISHIMOTO
REFERENCES
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 1:411–417.
2. Fitzgerald PH, Pickering AF, Eiby JR (1971): Clonal origin of thePhiladelphia chromosome and chronic leukaemia. Evidencefrom a sex chromosome mosaic. Br J Haematol 21:473–480.
3. Oguma N, Takemoto M, Oda K, Tanaka K, Shigeta C, SakataniK, Kanda N, Kuramoto A (1989): Chromic myelogeneous leu-kemia and Klinefelter’s syndrome. Eur J Haematol 42:207–208.
4. Hasle H, Mellemgaard A, Nielsen J, Hansen J (1995): Cancerincidence in men with Klinefelter syndrome. Br J Cancer71:416–420.
5. Mamunes P, Lapidus PH, Abbott JA, Roath S. (1961) Acuteleukaemia and Klinefelter’s syndrome. Lancet II:26–27.
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T. Yano et al.
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 145:148–150.
7. Shaw MP, Eden OB, Grace E, Ellis PM (1992): Acute lympho-blastic leukemia and Klinefelter’s syndrome. Pediatr HematolOncol 9:81–85.
Table 1
Results of cytogenetic study
KaryotypeNumber of cellsanalyzed
On admission 47,XXY,t(9;22;11)(q34;q11;q13)
10
46,XY 647,XXY 4
After induction Tx 46,XY 1047,XXY 947,XXY,add(2)
(p23)1
After 2nd consolidation Tx 47,XXY 1947,XXY,
2
16,
1
mar1
All cells were examined by G-banding technique.
Abbreviation
: Tx, therapy.
