Hematologic malignancies and Klinefelter syndrome: a chance association?

  • Published on
    15-Sep-2016

  • View
    219

  • Download
    0

Transcript

  • Cancer Genetics and Cytogenetics 139 (2002) 913

    0165-4608/02/$ see front matter 2002 Elsevier Science Inc. All rights reserved.PII: S0165-4608(02)00626-X

    Hematologic malignancies and Klinefelter syndrome:a chance association?

    Yi-Kong Keung

    a,*

    , David Buss

    b

    , Allen Chauvenet

    c

    , Mark Pettenati

    d

    a

    Section of Hematology-Oncology, Comprehensive Cancer Center of Wake Forest University, Medical Center Boulevard,Winston-Salem, NC 27157-1082, USA

    b

    Department of Pathology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1082 USA

    c

    Department of Pediatrics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1082 USA

    d

    Cytogenetic Laboratory, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1082 USA

    Received 12 April 2002; received in revised form 21 May 2002; accepted 22 May 2002

    Abstract

    Klinefelter syndrome was first described in 1942 as an endocrine disorder characterized by gynecomastia,hypogonadism, small testes, and elevated levels of follicle-stimulating hormone. An extra X chromosome(i.e., 47,XXY) was subsequently demonstrated in these patients and an increased incidence of leukemia

    and lymphoma has been described. We report a retrospective study of a series of unselected

    patients withKlinefelter syndrome diagnosed by cytogenetic studies and the occurrence of hematologic malignancies.

    The literature is also reviewed. 2002 Elsevier Science Inc. All rights reserved.

    1. Introduction

    Klinefelter syndrome (KS) was first described in 1942 asan endocrine disorder characterized by gynecomastia, hy-pogonadism, small testes, and elevated levels follicle-stimu-lating hormone (FSH). An extra X chromosome (i.e.,47,XXY) was subsequently demonstrated in these patients[1]. These patients tend to have an increased risk of devel-oping male breast cancer and mediastinal germ cell tumor[26]. Leukemia and lymphoma are not infrequent amongthese patients. We report a retrospective study of a series ofunselected patients with KS diagnosed by cytogenetic stud-ies and occurrence of hematologic malignancies.

    2. Materials and methods

    Patients with KS (i.e., 47,XXY) were identified from thedatabase of the Cytogenetic Laboratory in this institutionfrom January 1992 through April 2001. The medical recordsof these patients were reviewed.

    Review of medical literature was performed by searchingMEDLINE using keywords Klinefelter syndrome andlymphoma or leukemia as well as the references quotedin these articles.

    3. Results

    Forty-two patients were diagnosed with KS by virtue ofthe karyotype of 47,XXY in their peripheral blood or bonemarrow from January 1992 to April 2001. Prenatal cases of47,XXY diagnosed by amniocentesis were excluded in thisstudy. Eleven cases were deemed nonevaluable because theywere referred for cytogenetic studies only and no medicalrecords were available for review. Among these 11 cases, a22-year-old patient had complex cytogenetic abnormalitiesin the bone marrow specimen, 48,XXY

    c

    ,

    der(1)t(1;21)(p11;p11.2),

    5,der(7)t(1;7)(p11;p11.2),

    11,

    del(11)(q13),

    13,

    20[20]/47,XXY

    c

    [4], consistent with myelodysplas-tic syndrome or acute leukemia.

    The medical records of the remaining 31 cases were re-viewed. The median age at the time of diagnosis was 19.7(range 068.3). The initial cytogenetic studies were per-formed with peripheral blood specimens in all except fourcases in which KS was established in bone marrow speci-mens. Among the four bone marrow cases, one patient wasdiagnosed with anemia of chronic disease, and the otherthree patients had Ki-1 anaplastic large-cell lymphoma, my-elodysplastic syndrome, and acute lymphoblastic leukemia.The latter three cases are described in further detail below.

    3.1. Case 1

    A 29-year-old male presented in February 2000 with bi-lateral groin lymphadenopathy. Excisional biopsy demon-

    * Corresponding author. Tel.: (336) 716-7972; fax: (336) 716-5687.

    E-mail address

    : ykeung@wfubmc.edu (Y.-K. Keung).

  • 10

    Y.K. Keung et al. / Cancer Genetics and Cytogenetics 139 (2002) 913

    strated CD30

    anaplastic large-cell lymphoma. Bilateralbone marrow examination at the time of diagnosis was nor-mal. He received six cycles of cyclophosphamide, adriamy-cin, oncovin (vincristine), and prednisone (CHOP) followedby radiation to bilateral inguinal lymph nodes. Pathologicallyconfirmed recurrent disease involving right cervical nodeswas diagnosed a year later. Computerized tomography of thechest, abdomen, and pelvis was normal. He was referred tothis institution for consideration of autologous stem celltransplantation. Physical examination demonstrated enlargedcervical nodes. Genital examination was significant for smalltestes. There was no gynecomastia. Restaging bone marrowexamination was again normal. Cytogenetic study of the bonemarrow demonstrated 47,XXY

    c

    [20]; the same karyotype wasalso detected in the peripheral blood. Serum luteinizing hor-mone (LH) and FSH levels were elevated to 33.3 mIU/mL(normal 0.910.6) and 39.6 mIU/mL (normal 217.7). Test-osterone was 223 ng/dL (normal 2701194). He underwenthigh-dose cyclophosphamide and busulfan followed by autol-ogous stem cell transplant with prompt engraftment by day10. He was free of recurrence 6 months after transplant.

    3.2. Case 2

    A 2 1/2-year-old male presented with limping gait andspontaneous gingival bleeding. Physical examination re-vealed no lymphadenopathy or hepatosplenomegaly. Whiteblood cell (WBC) count was 3,200/

    L, with 15% neutro-phils, 70% lymphocytes, and 10% monocytes; hemoglobinwas 8.4 gm/dL and platelet count was 95,000/

    L. Bonemarrow examination revealed pre-B acute lymphoblasticleukemia. The cytogenetic study of the bone marrow re-vealed 47,XXY

    c

    [16]/54,XXY

    c

    ,

    4,

    8,

    9,

    12,

    17,

    18,

    21[3]. Peripheral blood karyotype was 47,XXY

    c

    , and sowas the bone marrow karyotype that was repeated aftercomplete remission was achieved. He was treated with che-motherapy and has been in remission for 2.75 years.

    3.3. Case 3

    A 31-year-old male presented in April 1996 with generalmalaise, vomiting, and dehydration. WBC was 8800/

    L, with16% neutrophils, 62% lymphocytes, and 14% blasts; hemoglo-bin was 13.8 and platelet count was 206,000/

    L. Serumsodium was 150 mg/dL, creatinine 1.3 mg/dL, blood urea ni-trogen 12 mg/dL, and uric acid 9.5 mg/dL. Bone marrow ex-amination revealed a hypocellular marrow with 20% myelo-blasts and trilineage dysplasia, consistent with refractory ane-mia with excess of blasts in transformation. Cytogenetic studyof the bone marrow showed 46,XXY

    c

    , inv(3)(q21q26),

    7[18]/47,XXY

    c

    [2]. His disease failed to respond to induction of che-motherapy with cytarabine and doxorubicin. He was then re-ferred to this institution for further management. On presenta-tion, serum sodium was 157 mg/dL, creatinine 2.1 mg/dL, anduric acid 9.1 mg/dL. Central diabetes insipidus (DI) was subse-quently diagnosed and was successfully treated with desmo-pressin (DDAVP

    )

    . Magnetic resonance imaging of the braindid not reveal any pituitary or hypothalamic lesion. Cere-brospinal fluid analysis and cytology were normal. Serum LHlevel was 27.3 mIU/mL. Complete remission was obtained af-ter reinduction with high-dose cytarabine, mitoxantrone, and

    L

    -asparaginase. Bone marrow cytogenetic study at the time ofremission revealed 47, XXY

    c

    [20]. The patient received high-dose cyclophosphamide and fractionated total body radiationfollowed by HLA-matched bone marrow transplantation inOctober 1996 from an unrelated male donor. By day 36 aftertransplant, he developed refractory graft versus host disease ofthe skin and gastrointestinal tract despite vigorous immunosup-pressive therapies and he finally succumbed to pneumonia 2months after transplant.

    Thirty-seven case reports of hematologic malignancies(7 cases of lymphoma and 30 cases of leukemia and myelo-dysplastic syndrome) are identified and summarized in Ta-bles 1 and 2, respectively. The median age at diagnosis oflymphoma is 39 years (range 3.7581), acute leukemia/

    Table 1Case reports of lymphoma associated with Klinefelter syndrome

    Year Age HistologyKS pre- orpostdate NHL BM involved

    Karyotype Referenceno.PB BM Tumor

    1965 53 y RCS Same

    46,XY/47,XXY/48,XXXY

    [16]

    1974 46 y Low grade lymphoma Post

    46,XY/47,XXY

    [17]

    1986 47 y High grade B-cell Same

    46,XY/47,XXY

    [18]

    1987 10 y MGCT, 6wk after, malignanthistiocytosis

    Same Yes 47,XXY 48,XXY,

    mar

    [19]

    1990 33 y Immunoblastic B-cell lymphoma Pre No

    [20]1994 40 m B-lymphoblastic lymphoma Same No

    47,XXY 47,XXY [21]1997 81 y Low grade B-cell lymphoma Same Yes 46,XY/

    47,XXY47,XXY

    [22]

    Current 31 Anaplastic Ki-1 lymphoma Same No 47,XXY 47,XXY

    Case no.

    Abbreviations

    : BM, bone marrow; m, months; MGCT, mediastinal germ cell tumor; PB, peripheral blood; RCS, reticulum cell sarcoma; y, years; , notreported.

  • Y.K. Keung et al. / Cancer Genetics and Cytogenetics 139 (2002) 913

    11

    MDS is 16 years (range 9 days68 years), and chronic leu-kemia is 43 years (range 2769). In 29 cases (78%), the di-agnosis of KS was made concomitantly with the diagnosisof hematologic malignancies. Five cases were known tohave KS before the diagnosis of malignancy.

    4. Discussion

    Mamunes et al. described the first case of acute leukemiain a patient with KS [7]. Sporadic reports of leukemia andother hematologic malignancies have been reported sincethen, and these cases are summarized in this review. Amongpatients with constitutional chromosomal abnormalities, Al-

    imena et al. reported an increased frequency of leukemia;however, only one case of KS was included in that study [8].

    Horsman et al. reviewed the bone marrow cytogeneticstudies of more than 1200 male patients in British Columbia(population of 2 million) and found only one case of KS as-sociated with acute myelomonocytic leukemia. They con-cluded that acute leukemia and KS was a chance association[9]. Price et al. followed 466 patients with KS prospectivelyfor 25 years and found that 15 died of malignancies (9 lung,2 breast, 1 anal, and 1 pancreatic cancer; one multiple my-eloma; one lymphoma). No cases of leukemia were identi-fied [10]. Hasle et al. studied the incidence of cancer amonga cohort of 696 men with KS and found only one case ofchronic lymphocytic leukemia [11].

    Table 2Case reports of leukemia associated with Klinefelter syndrome

    YearAge(Y)

    KS pre- or postdated leukemia FAB Peripheral blood Bone marrow

    Referenceno.

    1961 36 Pre AML 47,XXY

    [7]1981 30 Pre AML-M2 47,XXY

    [23],[24] 64 Same AML-M1 47,XXY 47,XXY[10]34 Same AML-M2 47,XXY[14]/48,XXY,

    8 [5]/48,XXY,20q

    ,

    21[5]40 Same AML-M4 47,XXY[23] 47,XXY[26]

    1986 10 m Same AML-M7 47,XXY 47,XXY [25]1987 16 Same AMML 47,XXY 47,XXY [9]1992 7 m Same AML-M5a 47,XXY 46,XXY,

    Y,t(10;11)(p13;q14) [26]1967 2.5 Same Acute leukemia,

    undifferentiated 47,XXY

    a

    46,XY[3]/47,XXY[23]/hyperploidy

    47[3] [27]

    1974 19 Same ALL 48,XXXY

    [28]1984 9d Same ALL-L2 47,XXY

    [29]1992 21 m Same ALL 47,XXY 47,XXY [30]

    42 m Same ALL 46,XY/47,XXY 46,XY/47,XXY1994 4 Same ALL-L2 47,XXY 47,XXY [31]2000 49 Same ALL-L2 46,XY/47,XXY 47,XXY,t(9;22;11)(q34;q11.2;q13) [32]1986 68 Same MDS, RARS 47,XXY 47,XXY/45

    46,XXY,

    5,

    7,

    12,

    21,del(3p),

    21,t(7;21),t(3;12),

    mar1,

    mar2[cp] [33]

    1993 40 Same MDS, 1 m later 2

    AML 47,XXY

    b

    47,XXY/47,XXY,del(2)(q13),del(3)(q12),del(5)(q13q33),

    7,

    12,der(17)(p11),

    3mar [34]

    1981 51 Same PRV, 14 y later 2

    AML-M4 47,XXY 47,XXY[20] [23],[24]1982 14 Same MGCT, 18 m later 2

    AML 47,XXY/50,XY,

    A,

    A,

    D,

    D47,XXY/50,XY,

    A,

    A,

    D,

    D [35]

    1990 16 Same MGCT concomitant with AML-M5

    47,XXY/48,XXY,

    i(12p) [36]

    1994 15 Same MGCT, 6 m later 2

    AML-M6 47,XXY 50,XXY,

    4,

    5,

    11,

    17,

    21,

    4mar [37]1961 59 Same CML 47,XXY

    c

    46,XY[3]/47,XXY [5] 46,XY,Ph[14]/47,XXY,Ph[2](peripheral blood)

    [38]

    1971 69 Same CML 46,XY/47,XXY 46,XY,Ph/47,XXY [39]1985 41

    CML 47,XXY 47,XXY,Ph/53,XXY,Ph,

    X,

    4,

    8,

    18,

    18,

    22q

    [8]1986 43 Post CML blast crisis

    47,XXY,Ph,

    Ph,

    mar/47,XXY,Ph [40]1989 27 Pre CML 46,XY/47,XXY 47,XXY,t(9;22)(q34;q11) [41]1990 35 Same CML 47,XXY 47,XXY,t(9;22)(q34;q11) [42]1978 69 Same MPD 46,XY/47,XXY 47,XXY/47,XXY,20q

    [43]1991 41 Pre Prostate CA, 2 y later CLL 47,XXY 47,XXY [44]1978 60 Same T-CLL 47,XXY

    a

    47,XXY,-8,

    14,

    18,

    t(3;8),

    t(11;14),

    i(18q),11q

    [45]Current 2.5 Same ALL-L1 47,XXY 47,XXY[16]/54,XXY,

    4,

    8,

    9,

    12,

    17,

    18,

    21[3] Case 2Current 32 Same RAEB

    47,XXY[2]/46,XXY,inv(3)(q21q26),

    7[18] Case 3

    a

    Buccal smear.

    b

    Bone marrow fibroblast.

    cSkin fibroblasts.Abbreviations: FAB, FrenchAmericanBritish classification; m, months; MGCT, mediastinal germ cell tumor; MPD, myeloproliferative disorder;

    Ph, Philadelphia chromosome; PRV, polycthemia rubra vera; y, years.

  • 12 Y.K. Keung et al. / Cancer Genetics and Cytogenetics 139 (2002) 913

    In the current study of 31 patients with KS, two cases ofacute leukemia were encountered. This apparent increase inthe prevalence of acute leukemia is intriguing. We believe,however, that this increase is at least partly due to of the in-creased frequency of cytogenetic studies in the patients withhematologic malignancies.

    From January 1992 to April 2001, 517 male patients withacute leukemia have been diagnosed and treated in this in-stitution. Every patient had at least one cytogenetic study ofthe bone marrow. Assuming the incidence of KS in a nor-mal male population is 1:500 [1214], one would expect tosee one case of KS among our male patients with acute leu-kemia. Furthermore, as demonstrated in Tables 1 and 2,78% of cases had KS diagnosed concomitantly with lym-phoma or leukemia. It is conceivable that KS is more likelyto be discovered in medical conditions such as leukemiaand lymphoma, which routinely require cytogenetic studies.

    The covert nature of KS is further supported by recentstudy. While the prevalence of KS in male breast cancer wasestimated to be 2.6%, Hultborn et al. detected a threefold in-crease in the prevalence (7.5%) by using a more sensitive fluo-rescent in situ hybridization technique in 93 male breast cancerpatients [3,4,15]. In view of KS being easily underdiagnosed,the current epidemiologic studies should be interpreted withcaution. Larger studies are required to confirm or disprove theassociation of KS and hematologic malignancies.

    References[1] Klinefelter HF. Klinefelter syndrome: historical background and de-

    velopment. South Med J 1986;79:108993.[2] Harnden DG, Maclean N, Langlands AO. Carcinoma of the breast

    and Klinefelter syndrome. J Med Genet 1971;8:4601.[3] Scheike O, Visfeldt J, Petersen B. Male breast cancer. 3. Breast carci-

    noma in association with the Klinefelter syndrome. Acta Pathol Mi-crobiol Scand [A] 1973;81:3528.

    [4] Evans DB, Crichlow RW. Carcinoma of the male breast and Klinefeltersyndrome: is there an association? CA Cancer J Clin 1987;37:24651.

    [5] Nichols CR. Mediastinal germ cell tumors. Semin Thorac CardiovascSurg 1992;4:4550.

    [6] Nichols CR, Heerema NA, Palmer C, Loehrer PJ Sr, Williams SD,Einhorn LH. Klinefelter syndrome associated with mediastinal germcell neoplasms. J Clin Oncol 1987;5:12904.

    [7] Mamunes P. Acute leukemia and Klinefelter syndrome. Lancet 1961;ii:267.

    [8] Alimena G, Billstrom R, Casalone R, Gallo E, Mitelman F, Pasquali F.Cytogenetic pattern in leukemic cells of patients with constitutionalchromosome anomalies. Cancer Genet Cytogenet 1985;16:20718.

    [9] Horsman DE, Pantzar JT, Dill FJ, Kalousek DK. Klinefelter syn-drome and acute leukemia. Cancer Genet Cytogenet 1987;26:3756.

    [10] Price WH, Clayton JF, Wilson J, Collyer S, De Mey R. Causes ofdeath in X chromatin positive males (Klinefelter syndrome). J Epide-miol Community Health 1985;39:3306.

    [11] Hasle H, Mellemgaard A, Nielsen J, Hansen J. Cancer incidence inmen with Klinefelter syndrome. Br J Cancer 1995;71:41620.

    [12] Jacobs PA. The incidence and etiology of sex chromosome abnormal-ities in man. Birth Defects Orig Artic Ser 1979;15:314.

    [13] Gerald PS. Sex chromosome disorders. N Engl J Med 1976;294:7068.[14] Nielsen J, Wohlert M. Sex chromosome abnormalities found among

    34,910 newborn children: results from a 13-year incidence study inArhus. Birth Defects Orig Artic Ser 1990;26:20923.

    [15] Hultborn R, Hanson C, Kopf I, Verbiene I, Warnhammar E, Weima-rck A. Prevalence of Klinefelter syndrome in male breast cancer pa-tients. Anticancer Res 1997;17:42937.

    [16] MacSween RNM. Reticulum cell sarcoma and rheumatoid arthritis ina patient with XY/XXY/XXXY Klinefelter syndrome and normal in-telligence. Lancet 1965;i:4601.

    [17] Tsung SH, Heckman MG. Klinefelter syndrome, immunological dis-orders, and malignant neoplasm: report of a case. Arch Pathol LabMed 1974;98:3514.

    [18] Becher R. Klinefelter syndrome and malignant lymphoma. CancerGenet Cytogenet 1986;21:2713.

    [19] Beasley SW, Tiedemann K, Howat A, Werther G, Auldist AW,Tuohy P. Precocious puberty associated with malignant thoracic ter-atoma and malignant histiocytosis in a child with Klinefelter syn-drome. Med Pediatr Oncol 1987;15:27780.

    [20] Liang R, Woo E, Ho F, Collins R, Choy D, Ma J. Klinefelter syn-drome and primary central nervous system lymphoma. Med PediatrOncol 1990;18:2369.

    [21] Attard-Montalto SP, Schuller I, Lastowska MA, Gibbons B, KingstonJE, Eden OB. Non-Hodgkins lymphoma and Klinefelter syndrome.Pediatr Hematol Oncol 1994;11:197200.

    [22] Humphreys M, Lavery P, Morris C, Nevin N. Klinefelter syndromeand non-Hodgkin lymphoma. Cancer Genet Cytogenet 1997;97:1113.

    [23] Geraedts JP, Mol A, Briet E, Hartgrink-Groeneveld CA, den Ottolan-der GJ. Klinefelter syndrome: predisposition to acute non-lympho-cytic leukaemia? Lancet 1980;1:774.

    [24] Muts-Homsma SJ, Muller HP, Geraedst JP. Klinefelter syndrome andacute non-lymphocytic leukemia. Blut 1982;44:1520.

    [25] Phebus CK, Berg SL. Acute megakaryoblastic leukemia and Klinefeltersyndrome. Am J Pediatr Hematol Oncol 1986;8:2602.

    [26] Foot AB, Oakhill A, Kitchen C. Acute monoblastic leukemia of in-fancy in Klinefelter syndrome. Cancer Genet Cytogenet 1992;61:99100.

    [27] Borges WH, Nicklas JW, Hamm CW. Prezygotic determinants inacute leukemia. J Pediatr 1967;70:1804.

    [28] Sohn KY, Boggs DR. Klinefelter syndrome, LSD usage and acutelymphoblastic leukemia. Clin Genet 1974;6:202.

    [29] Gale GB, Toledano SR. Congenital acute lymphocytic leukemia in anewborn with Klinefelter syndrome. Am J Pediatr Hematol Oncol1984;6:3389.

    [30] Shaw MP, Eden OB, Grace E, Ellis PM. Acute lymphoblastic leuke-mia and Klinefelter syndrome. Pediatr Hematol Oncol 1992;9:815.

    [31] Gurgey A, Kara A, Tuncer M, Alikasifoglu M, Tuncbilek E. Acutelymphoblastic leukemia associated with Klinefelter syndrome. Pedi-atr Hematol Oncol 1994;11:2279.

    [32] Yano T, Yuzurio S, Kimura K, Kshimoto T. Ph-positive acute lym-phocytic leukemia in a man with Klinefelter syndrome. Cancer GenetCytogenet 2000;118:834.

    [33] Abidi SM, Griffiths M, Oscier DG, Mufti GJ, Hamblin TJ. Primarymyelodysplastic syndrome with complex chromosomal rearrange-ments in a patient with Klinefelter syndrome. J Med Genet 1986;23:1835.

    [34] Dow G, Reid GD, Horsman DE, Barnett MJ. Unusual rheumatologi-cal and cardiological manifestations of acute myelogenous leukemiain a patient with Klinefelter syndrome. Leuk Lymphoma 1993;9:41921.

    [35] Penchansky L, Krause JR. Acute leukemia following a malignant ter-atoma in a child with Klinefelter syndrome: case report and review ofsecondary leukemias in children following treatment of a primaryneoplasm. Cancer 1982;50:6849.

    [36] Ladanyi M, Samaniego F, Reuter VE, Motzer RJ, Jhanwar SC, BoslGJ, Chaganti RS. Cytogenetic and immunohistochemical evidencefor the germ cell origin of a subset of acute leukemias associated withmediastinal germ cell tumors. J Natl Cancer Inst 1990;82:2217.

    [37] Aurer I, Nemet, Uzarevic B, Hitrec V, Mrsic S, Grgic M, Boban D,Zupancic-Salek S, Radman I, Labar B. Mediastinal malignant ter-atoma and acute myeloid leukemia in a patient with Klinefelter syn-dromecomparison of DNA content in the two malignancies. ActaOncologica 1994;33:7056.

  • Y.K. Keung et al. / Cancer Genetics and Cytogenetics 139 (2002) 913 13

    [38] Tough IM, Brown WMC, Baikie AG, Buckton KE, Harnden DG, JacobsPA, King MJ, McBride JA. Cytogenetic studies in chronic myeloid leuke-mia and acute leukemia associated with monogolism. Lancet 1961;i:411.

    [39] Fitzgerald PH, Pickering AF, Eiby JR. Clonal origin of the Philadel-phia chromosome and chronic myeloid leukaemia: evidence from asex chromosome mosaic. Br J Haematol 1971;21:47380.

    [40] Singh S, Wass J, Vincent PC, Young GA, Gunz FW. Significance of second-ary cytogenetic changes in patients with Ph-positive chronic granulocyticleukemia in the acute phase. Cancer Genet Cytogenet 1986;21:20920.

    [41] Oguma N, Takemoto M, Oda K, Tanaka K, Shigeta C, Sakatani K,Kamada N, Kuramoto A. Chronic myelogenous leukemia andKlinefelter syndrome. Eur J Haematol 1989;42:2078.

    [42] Adhvaryu SG, Jani KH, Balar DB, Shah PM. Klinefelter syndromepatient with chronic myelogenous leukemia. Cancer Genet Cytogenet1990;48:1357.

    [43] Testa JR, Kinnealey A, Rowley JD, Golde DW, Potter D. Deletion ofthe long arm of chromosome 20 [del(20)(q11)] in myeloid disorders.Blood 1978;52:86877.

    [44] Pienkos EJ, Meisner LF. Adenocarcinoma of the prostate in a 41-year-old man with XXY karyotype and chronic lymphocytic leuke-mia: report of a case. J Urol 1991;145:14850.

    [45] Finan J, Daniele R, Rowlands D, Nowell P. Cytogenetics of chronic Tcell leukemia, including two patients with a 14q translocation. Vir-chows Arch B Cell Pathol 1978;29:1217.

Recommended

View more >