Cytogenetic Studies and Clinical Aspects of Patients with Plasma Cell Leukemia and Leukemic Macroglobulinemia 1

[CANCER RESEARCH 43, 905-912, February 1983] 0008-5472/83/0043-0000502.00 Cytogenetic Studies and Clinical Aspects of Patients with Plasma Cell Leukemia and Leukemic Macroglobulinemia 1

Yoshimi Ueshima, 2 Shirou Fukuhara, Kenichi Nagai, Kiyoshi Takatsuki, and Haruto Uchino

First Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, 54-Shogoin Kawaramachi, Sakyo-ku, Kyoto 606 [Y. U., S. F., K. N., H. U.], and Second Division, Department of Internal Medicine, Faculty of Medicine, Kumamoto University, Kumamoto [K. T.], Japan

ABSTRACT evolution of myeloma cells (1 6). This assumption remains ten- tative because of lack of data in PCL. Chromosomes of six patients with plasma cell leukemia and We, rc, nnrt fh~ nhrnmns s163 ~ncl fh# r:linir~l ~ncl one patient with leukemic macroglobulinemia were examined ..... r ...... morphological features in 6 patients with PCL and in one from peripheral blood, bone marrow, and/or pleural fluid. All patient with leukemic MG. The karyotypic differences between the patients had a clonal chromosomal abnormality. The modal these patients and reported cases of leukemias, malignant chromosome number was near tetraploid in two, pseudodiploid lymphomas, and MM are discussed. in two, and hypodiploid in three patients. Rearrangements of chromosome 1 were found in all the patients. The most consistent abnormality was a large marker involving the long arm MATERIALS AND METHODS of No. 1, found in six patients, including the patient with Chromosomes of 6 patients with PCL and one patient with leukemic macroglobulinemia. Each patient had one to four large markers MG were examined from peripheral blood, bone marrow, and/or which resulted in partial trisomy to hexasomy for the long arm pleural effusion specimens. PCL was defined as more than 0.5 x 109 of No. 1. The translocations occurred with No. 9 in two, with circulating plasma cells or plasmoblasts per liter. The peripheral blood No. 1 6 in two, and Nos. 8, 1 7, and 1 8 each in one patient. The mononuclear cells were separated with Ficoll-sodium metrizoate gra- survival time from the diagnosis was less than 1 year in five of dient centrifugation and were cultured in Roswell Park Memorial Insti- them and over 2 years in one. The only patient whose cells tute Medium 1640 containing 10% fetal calf serum at 37 ~ for 24 to 48 lacked an extra lq lived for over 3 years. Five 14q+ marker hr in 5% CO2. Bone marrow and pleural fluid samples were processed directly without prior culture. Mitotic cells were arrested with 1 x 10 -6 chromosomes were detected in three patients. The donor chro- M colchicine for 2 hr, treated with 0.075 M KCI for 10 to 30 min, and mosome was No. 1 1 in one of these and was undetermined in subsequently fixed in methanol:acetic acid (3:1). Air-dried slides were the others; the size of each 14q+ marker seemed quite differ- first stained with Giemsa and then photographed; after destaining, the ent which suggested different donor chromosomes. Loss of a same cells were restained with quinacrine mustard and photographed sex chromosome was found in five patients. Loss of No. 13 with a fluorescence microscope. Case 1 was banded with a G-banding and gain of No. 7 or 7q were each found in two patients. method (21). Descriptions of the chromosomes follow the recommen- Rearrangement or deletion of the short arm of No. 8 was found dations of the ISCN (1978) (9). in five patients. A rearrangement of 9p was found in three patients. The myeloma cells had a different morphology in the peripheral blood, bone marrow, and/or pleural fluid before and RESULTS after the leukemic phase of one patient; however, chromosome Clinical data on the 7 patients are presented in Table 1. Four analysis revealed the same clone despite the altered morphol- patients had PCL at the time of initial diagnosis, and in 2 ogy. patients (Cases 1 and 5) a leukemic phase subsequently de- veloped. The patient with MG (Case 7) also had leukemic INTRODUCTION plasmacytoid cells at diagnosis. The survival after diagnosis was less than 1 year in 5 patients and over 2 years in 2. All the PCL 3 is an infrequent phase in MM. The clinical course may patients had anemia, hypercalcemia, and renal insufficiency. be fulminant with features resembling those of acute leukemia, Three had hepatosplenomegaly (Cases 1, 2, and 5), and 3 and it is sometimes recognized as a distinct subentity (28). (Cases 2, 5, and 6) had pleural effusion with plasma cell Chromosome studies in patients with MM and related parapro- invasion. In addition, one had progressive lower limb paresis teinemic disorders have often been reported (1,3, 1 0, 1 1, 1 5, (Case 2), one had meningeal involvement (Case 5), and another 16, 22, 23, 26, 29), but there are few reports of PCL (8, 1 1, had obstructive jaundice with plasma cell invasion (Case 6). 16, 26). In MM, the pattern of chromosome aberrations has Postmortem examination in 3 patients (Cases 1, 2, and 5) b,~en quite variable, and no consistent markers were noted in showed very extensive infiltration of the marrow, liver, lymph the published data. On the other hand, it has been suggested nodes, lungs, and other organs with plasma cells. that the 14q+ marker may be necessary for the leukemic Cytogenetic data are presented in Table 2. Chromosomes were studied before treatment in 2 patients, after treatment in Supported in part by a grant from the Ministry of Welfare of Japan. 4 patients, and before and after treatment in one patient. There 2 To whom requests for reprints should be addressed, at M.D. Department of were no clear differences between the karyotypes of untreated Internal Medicine, Faculty of Medicine, Kyoto University, 54-Shogoin Kawara- machi, Sakyoku, Kyoto 606, Japan. Present address: M.D. Department of Med- patients and those of treated patients. All of the patients had a icine, Box 420, University of Chicago, Chicago, II1. 60637. clonal chromosomal abnormality. In 2 patients (Cases 1 and The abbreviations used are: PCL, plasma cell leukemia; MM, multiple mye- Ioma; MG, macroglobulinemia. 2), the cells from bone marrow, peripheral blood, and/or Received June 17, 1982; accepted October 11, 1982. pleural effusion had the same karyotype. In another patient

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Table 1 Clinical and hematological data in 6 patients with PCL and a patient with MG at diagnosis of PCL % of plasma cells WBC in pe- and atypical lym- Therapy before Survival after Age Serum para- ripheral blood phocytes in periph- chromosome ex- Total duration of chromosome ex- Case a Sex (yr) protein (x 109/liter) eral blood amination disease (mos.) amination (mos.) 1 (M. Y.) M 45 Absent 52.1 90 M, b P 39 2 2 (Y. N.) M 35 IgG~ 7.6 33 E, P 10 7 3 (S. I.) F 71 IgG• 9.7 72 None 1 1 4 iT. Y.) M 73 BJ~ 20.7 10 None 1.5 1.5 5 (N. Y.) M 45 IgGX 8.2 37 (1) None 8 (1) 8 (2) M, P (2) 4 (3) 0 6 (S. K.) F 64 IgAK 6.4 22 M, P 34 (1),31 (2) 2 7 (M. H.) M 71 IgMX 78.0 90. D, C, 6-MP, P 12 8

a Cases 1 to 6, PCL; Case 7, MG. b M, melphalan; P, prednisone; E, endoxan; D, daunomycin; C, 1-/~-D-arabinoside furanosylcytosine; 6-MP, 6-mercaptopurine.

Table 2 Chromosome patterns of patients with PCL and MG Date of chro- No. of cells ex- % of cells with Source of mosome stud- amined abnormal kary- Patient sample ies (banded) otype Modal karyotype 1 (M. Y.) BM a 9/21/77 20 100 44,X,-Y,-21,-22,1p-,+1q-,t(11 ;14)(ql 1 ;q32),14q+ PB 10/15/77 19 1 O0 44,X,-Y,-21,-22,1 p-, + 1q-,t(11 ;14)(ql 1 ;q32), 14q+ 2 (Y. N.) BM 4/12/79 16 100 44,X,-Y,-9,- 13,t(6;8)(q 13;pl 1 ), + der(9)t(1 ;9)(1 qter--> 1 ql 2::1 q44--* 1 ql 2: :9q34--> 9pter) PB 4/12/79 9 100 44,X,-Y,-9,- 13,t(6;8)(q 13;pl 1 ), + der(9)t(1 ;9) PE 4/12/79 7 86 44,X,-Y,-9,-13,t(6;8)(q 13;pl 1 ), + der(9)t(1 ;9) 3 (S. I.) PB 10/25/79 40 20 43,X,-X,- 1,-8,-9,- 1 O,- 13,- 22, + der(8)t(1 ;8)(1 qter---*cen--,8qter), +der(9)t(1 ;9)(1 qter--* 1q21 ::9p24--*9qter), + der(10)t(1 ;10) (10pter-* 10q26:: 1 p31--* 1 pter), + t(1 ; ?)(q 12;?) 4(T. Y.) PB 12/26/79 38 76 78,XX,-Y, +4,+5,+7,+ 7,+ 7,+7, +8, +8,+ 10,+ 12, + 12, + 16,+ 18,+ 19,+ 19,+21, +21,+3q+,+3q+,+3p-,+9p+,+9p+,+11p+,+11p+,+14q+,+14q+, + 1 6p +, + 16p+, + del(1 )(q21 ), + del(1 )(q21 ), + der(17)t(1 ; 17) (1 qter--->1 ql 2::17pl 3-,17qter), + der(17)t(1 ;17) 5 (N. u BM 1/12/80 14 85 46,XY,- 16,- 18,del(6)(q21 ), + der(16)t(1 ;16)(1 qter-* 1 q21 :: 16pl 3--->16qter), + marl PB 5/21/80 16 100 46,XY, - 16, - 18,del(6)(q21 ), + der(16)t(1 ;16), + marl PE 9/06/80 20 100 47,XY,-8,- 15,- 16,- 18,del(6)(q21 ), + der(16)t(1 ;16), + t(8; 15)(8qter--*8p23::15ql 2 --,15qter),14q+,+mar1 ,+mar2,+mar3/sdl (4 cells)47,XY, same, 4q+ 6(S. K.) PB 4/24/79 5 0 46,XX PE 8/05/81 27 100 86,XX,+3,+3,+4,+4,+5,+6,+6,+8,+8,+10,+11,+11,+12,+12,+14,+15, +18,+18,+19,+19,+20,+20,+21,+21,+2q+,+2q+, + 2xt(1 ; ?)(1 q 11 ; ?), + 2xt(1 ;?)(1 q 11 ;?), + 2xdup(7) (qter--*q22::p22-,qter), + 2xder(8)t(8p I 1 ; ?)+ 2xder(9)t(9; 13) (9qter--~9p23:: 13q 21--~ 13qter), + 4mar 7 (M. H.) PB 1/26/80 28 100 (1)46,Y- X, - 7, - 16, - 18, - 19,del(1 )(q21 ),del(5)(q23), + del(5)(q 23), +t(7;19)(7qter---> 7 p22:: 19ql 3-19pter),del(8)(p 12), + der(16)t(1 ;16)(1 qter--. 1 ql 2::16pl 3-->16qter), + der(18)t(1 ;18) (1 qter--->1 ql 2:: 18pl 1--->18qter),+ marl (2)45,Y,- X,- 7,- 18,- 19, del(1 )(q21 ),del(5)(q23), +t(7; 19)(p22;q 13),del(8)(p 12), + der(18)t(1 ;18),2q-,2q+, +marl

a BM, bone marrow; PB, peripheral blood; PE, pleural effusion.

(Case 5), the original abnormal karyotype showed additional short arm of No. 8 was found in 4 patients, and an 8p- structural rearrangements in the pleural fluid obtained 8 months chromosome was found in one. The break point in 8p was near later. the centromere in 3 patients, pl 2 in one and p23 in the other The modal chromosome number was hyperdiploid in 3, pseu- patient. A rearrangement of the short arm of No. 9 was found dodiploid in 2, and tetraploid in 2 patients. All the patients had in 3 patients and a rearrangement of the long arm of No. 9 was an abnormality of chromosome 1, and 6 of them had one to 4 found in one patient. The break point of 9p was p23 in one large markers involving the long arm of chromosome 1, which patient, p24 in the second, and undetermined in the third. Two resulted in partial trisomy to hexasomy for the long arm of patients with near tetraploid chromosome numbers each had chromosome 1. The rearranged lq was translocated to No. 9 2 extra No. 7 chromosomes or 7q chromosomes: segment in 2; to Nos. 8, 1 6, or 1 7 each in one patient with PCL; to Nos. q21-qter, in addition to the tetraploidy. Five patients showed 16 and 18 in the patient with MG; and was undetermined in loss of a sex chromosome; there was loss of an X in one female one patient (Case 6). The break points in No. 1 were q21 in 2 and one male and loss of a Y in 3 males. A loss of No. 13 and of the markers and near the centromere in 9 of the markers a loss of No. 22 was each found in 2 patients. involving lq. The 14q+ marker was found in 3 patients. Two patients each had two 1 4q + markers. The donor chromosome CASE REPORTS was No. 11 in one of the 14q+ markers in Case 1 (Fig. la) and was undetermined in others; but the size differed from Case 1. The clinical and immunological findings of Patient case to case (Figs. l a, lb, and 5). A rearrangement of the M. Y., a 45-year-old man, were already reported (24). Cyto-

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Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 1983 American Association for Cancer Research. Chromosomes in PCL genetic studies were performed after the leukemic phase de- when he noticed left chest pain. He was hospitalized in Decem- veloped. There was one normal No. 1, a lq-, and a 1p- ber 1979 because of mental confusion. He had hypercalcemia, chromosome. The centromere region seemed to be triplicated. anemia, leukocytosis, and serum monocIonal IgM, and the Two 14q+ chromosomes of differing size were present; the diagnosis of MG was made. He died in October 1980 from a origin of the extra material was 11q in one of them and generalized infection. Chromosomes were studied 1 month remained unclear in another (Fig. la). after admission. No cells had a normal X, but it was possible Case 2. Patient Y. N., a 35-year-old man, first noted high that the X chromosome was involved in the marker (Fig. ld). fever in December 1978, and PCL was diagnosed in February The long arm of No. 1; segment q12-qter was trisomic and 1979. He died in November 1979 from systemic complication ql 2-q21 was tetrasomic in about one-half of the cells. of infection. Postmortem examination showed plasma cell tu- mors in the base of the skull, vertebra, ribs, lungs, kidneys, DISCUSSION liver, and pleura. The plasma cells were small and ovoid in the peripheral blood and were somewhat immature in the bone Chromosome studies in our series revealed a high incidence marrow and the pleural fluid. of clonal chromosomal abnormalities in PCL. Four series of Chromosome studies for bone marrow, peripheral blood, and prebanding studies (1, 3, 10, 23) and 2 series of banding pleural fluid were performed after 2 cycles of endoxan and studies containing 10 or more cases of plasma cell dyscrasia prednisone therapy. The long arm of No. 1 was tetrasomic as have been published (11, 16, 29). The incidence of chromo- the result of a large marker which included No. 9 and a somal abnormalities varied from 28 to 87%. In stable MM, duplicated lq (Fig. 2). myeloma cells in division occur much less frequently than do Case 3. Patient S. I. first noted general malaise and was their normal counterparts, because of their long generation admitted to the hospital with a diagnosis of PCL. She died 1 time (11 ). In the accelerated phase of MM, a higher percentage month after admission because of a sudden cerebral hemor- of abnormal karyotypes has been reported (11), but it is still rhage. The plasma cells in the bone marrow and peripheral difficult to estimate the overall frequency. The high incidence blood were small and immature with scanty cytoplasm, but in our series could be due to the accelerated clinical stage in some of them were somewhat larger than the others. An the cases; we could, therefore, study the spontaneously divid- abnormal clone was found in about 20% of the cells (Fig. 3). ing myeloma cells. There were one normal No. 1 and 3 large markers involving The frequent involvement of No. 1 and the presence of the the long arm of No. 1 which were translocated to Nos. 8, 9, large marker chromosomes involving the long arm of No. 1 and an undetermined chromosome. One chromosome 10 had seemed to be characteristic of MM, especially in the leukemic extra material on the long arm, the origin of which was I p. phase of MM. All 7 cases including the case of MG had the Case 4. Patient T. Y. first noted left precordial pain, back abnormalities of No. 1, and 6 of them had the large marker pain, nausea, and vomiting, and a diagnosis of PCL was made involving the lq in our series. The large markers involved the in December 1979. He had anemia, renal failure, and hepatic long arm of No. 1 and various other chromosomes. The trans- dysfunction and died 1.5 months later. Plasma cells in the locations occurred with Nos. 8, 9, 1 6, 17, and 18 in our series; peripheral blood were immature and atypical for plasma cells. Nos. 3 and 10 in the reported cases of PCL; and Nos. 12, 1 5, The cells with abnormal chromosomes were near tetraploid, and 16 in the MM series. Two large markers involving the lq and most of the markers were duplicated (Fig. lb). Two 14q+ were found in the patient with MG in our series. The translo- marker chromosomes in addition to 2 normal No. 14 chromo- cations occurred with Nos. 16 and 18. These markers seemed somes were observed which seemed to have a same donor to be similar to the markers seen in other patients with PCL. chromosome, but the origin was undetermined. Duplicated Thus, the large markers involving the lq could be common in large markers involving the I q and No. 1 7 were present. There MM, PCL, and MG. Although other large markers were present were 6 normal No. 7 chromosomes. which did not involve the lq, but involved No. 2 or No. 3 (Fig. Case 5. The clinical course of Patient N. Y. has been reported 1), it was suggested from our results that most of the large (12). The plasmacytoid cells in the bone marrow, peripheral markers may involve the long arm of No. 1 in MM and PCL. blood, and pleural fluid had different morphology (Fig. 4). The presence of the large marker chromosomes resulted in Cytogenetic studies were performed on 3 occasions. A large trisomy, tetrasomy, or hexasomy of the long arm of No. 1 in all marker involving the long arm of No. 1 and No. 16 was 6 cases with the large marker which involved the long arm of consistent in all specimens, while a translocation of No. 1 5 to No. 1. Rowley proposed that trisomy for bands 1q25-1q32 8p and an acrocentric marker appeared only in the pleural provides the affected cells with a proliferative advantage in fluid. The 14q+ marker was found in the cells from pleural various hematological disorders (17). In the MM series, the fluid, but it was unclear in the cells from bone marrow and significantly shorter survival time was reported for 5 patients peripheral blood (Fig. 5). with trisomy for the lql 2-1q3 section (16). In our series, 5 Case 6. The clinical course of Patient S. K. has been reported patients with an extra l q had a fulminant course and died (13). Chromosome studies were attempted on several occa- within 1 year, and only one lived for over 2 years. She had sions, but only 2 samples had mitotic cells. Most markers generalized plasmacytoma, however, and died 2 months after seemed to be duplicated (Fig. 1 c). Duplicated sets of a marker the chromosome study. involving the I q were present, but the other chromosome could Two of 7 cases of PCL in the literature have trisomy 1 q (11, not be determined. There were two normal No. 7 chromo- 16, 26) (Table 3). Their survival times are 41 and 1 3 months, somes, and two 7p+ chromosomes which contained a dupli- respectively, after diagnosis. The longer survival case had cated segment of 7q21 to 7qter. expanded infiltration of myeloma cells at the autopsy. Another Case 7. Patient M. H. was well until 1 month before admission had trisomy l q in the side line and died 1 month after the

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Table 3 Summary of karyotype and clinical course in patients with PCL Duration after Serum parapro- Totalduration chromosome ex- Ref. Diagnosis tein (mos.) amination(mos.) Modal karyotype Wurster-Hill et al. PCL 46,14q+,+mar (29) Liang et al. (11 ) PCL IgA 41 1 47,XY,dup(1 )(ql 1q32),t(1 ;10)(p22;pl 5), inv(6)(p21 ql 3),t(11 ;14)(q23;q32),21 p+, + 1mar Liang et al. (11 ) MM-PCL Absent 13 1 46,XY,inv ins(1 )(pter::q21 - p22?::p32?- p36:q21 - qter),t(11;14)(ql 31 ;q32) Philip et al. (16) PCL IgG 6 2 45,X,-Y,- 1, +t(1 ;3)(1 pter- 1q3::3q27or28or 29-3pter),-3,+11,14q+ sdl ;45,X,-Y, - 1,- 1, + 2t(1 ;1 )(1 pter- 1p3::1 q2-1 qter), -3,?14q+ Philip et al. (16) PCL IgG~ 37 37 47,XX,14q+ ,+mar 14q+;t(11 ;14)? Van Den Berghe PCL IgG~ 50 5 45,X,del(X)(q25?),t(3;8;22)(q13,q34,q 11 ), et al. (26) -5,-7,-10,-10,-11,del(13)(q137 q317),+ 16,19q+,+3mar Gahrton et al. (8) PCL IgG~+~ 7a 7a? 46,XX,t(1 ;6)(1 pter- 1p34:: 1p22-1 qter:: 1p34 - 1p22::6pter- 6qter),t(11 ;14)(ql 3;q32), - 14, + der(14)t(11 ;14) a Living.

chromosome examination. Thus, the rearrangement of No. 1, 14q+ marker, 5 had rearrangements or deletion of 8p, 3 had especially the gain of the long arm of No. 1, might be associated a rearrangement of 9p, 2 had extra No. 7 chromosomes or with leukemic evolution of myeloma cells. 7qs, and one had a 6q- chromosome. Loss of sex chromo- The 14q + marker has been recognized as the most consist- some was found in 5 patients, and loss of chromosomes 13 or ent structural aberration in PCL (1 1, 16, 29). Six of 7 cases of 22 was found in each of 2 patients. The loss of a sex chromo- PCL in the literature (8, 1 1, 16, 26, 29) have been reported to some has sometimes been found in other hematological can- have a 14q+ marker, and the remaining one is suspected to cers (20). The 14q+ chromosome, gain of No. 7 or 7q, and be a secondary leukemia, because she is missing chromo- the 6q- chromosome may be lymphoid markers which may be somes 5 and 7 (1 6, 26). Four of 18 patients with MM have a common in T-, B-, and non-T, non-B cancers (5, 6, 14, 1 8, 20, 1 4q + marker, and it has been suggested that the 14q + marker 25). The high incidence of the abnormalities of No. 1, especially is necessary for the evolution of B-cell leukemias (1 6). In our the large markers including 1 q, deletion or rearrangements of series, however, only 3 patients had the 14q + marker, and the 8p, rearrangement of 9p, and loss of No. 13, could be char- remaining 4 did not. The incidence of the 14q+ may be higher acteristics for PCL, MM, or B-cell cancers. in PCL than in MM, but the 14q+ chromosome does not appear Two series with banding containing 4 cases with PCL and to be necessary for leukemic evolution of myeloma cells. The 14 cases with MM with abnormal karyotypes have been re- identification of the donor chromosomes to 14q has been ported (1 1, 1 6). Although 5 other cases with PCL have been difficult in MM or PCL, because the banding pattern is often reported, 2 are cell line studies (2, 4). One was reported to poor, and the rearrangements are complex (1 1, 1 6). The origin have a 14q+ chromosome, but the details are lacking (29) and of the 14q+ has been determined as t(1 1 ;14) in 3 and possibly another case (26) could be secondary leukemia. The gain of t(1 1 ;14) in one patient with PCL and has not been determined No. 9 in MM is significantly higher than in the malignant in the remaining patients with MM or PCL (1 1, 1 6, 29). One of lymphoma series (p < 0.001). Nine of 14 patients with MM five 14q+ chromosomes from three patients in our series was have a gain of No. 9, compared with 3 of 114 cases with a t(1 1 ;14), but the others remained undetermined. The size lymphoma reviewed by Sandberg (20). No patient in our series and banding pattern of each 14q + chromosome differed from or in the reported cases of PCL had a gain of No. 9, and it the 14q+ originating from 1 lq, which suggests different do- could be one of the differences between PCL and MM, although nors. Our results suggest the 14q+ chromosomes in MM and the number is too small to be certain. Instead of the gain of No. PCL are not uniform as t(8;14) in Burkitt lymphoma, but some 9, a rearrangement of 9p was observed in 3 and a 9q+ was different donors may participate in the formation of the 14q+ observed in one patient in our series. Translocations occurred chromosomes. with the long arm of No. 1 in 3 of them. The rearrangement of It appears that almost every chromosome was involved and 9p could be one of the characteristics of PCL. that the chromosome pattern was variable both in our series In the MM series, the incidence of loss of No. 8 seems to be and in the reported cases of plasma cell dyscrasia. The pattern higher than in the lymphoma series. In the series of Liang et al. of the abnormalities, however, seemed to have some charac- (11), a missing No. 8 chromosome was reported in 4 of 6 teristic differences from that in myelogeneous leukemia, malig- patients with MM; in one of them, it was observed only in the nant lymphomas or lymphocytic leukemias. No cases in our second sample which was obtained 9 months after the first series showed a loss of No. 5 or No. 7 which have been often sample. In our series, 5 patients had rearrangements or dele- reported in acute myelogenous leukemia and secondary acute tions of 8p. One patient had a translocation of No. 15 to 8p; nonlymphocytic leukemia (19, 20, 27). No cases had an addi- this was noted in the third sample which was obtained 4 months tional No. 12 which has been suggested to be a consistent after the second sample. Thus, the loss of No. 8 or rearrange- aberration in chronic B-cell lymphocytic leukemia (7). Instead ment of No. 8 appears to be a common aberration associated of these, all 7 patients had abnormalities of No. 1, 3 had the with the karyotypic evolution of myeloma cells.

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We have shown that the markers involving lq and another 12. Nagai, K., Ohnaka, T., Ueda, Y., Takatsuki, K., and Uchino, H. Meningeal involvement in multiple myeloma. Acta Haematol. (Basel), 66: 39-43, 1981. chromosome and rearrangements or deletions of 8p or 9p are 13. Oguma, S., Nagai, K., Takatsuki, K., and Uchino, H. Extraosseous plasma- common in PCL. These are sometimes observed in MM but are cytoma causing obstructive jaundice: a rare case of IgA myeloma. Acta infrequent in other B-cell disorders. Other investigations have Haematol. Jpn., in press, 1983. 14. Oshimura, M., Freeman, A. I., and Sandberg, A. A. Chromosomes and identified different patterns in Burkitt's lymphoma where trans- causation of human cancer and leukemia. XXVI. Banding studies in acute locations commonly involve 8q and in poorly differentiated lymphoblastic leukemia (ALL). Cancer (Phila.), 40:1161-1171, 1977. lymphocytic lymphoma in which a t(1 4q+;1 8q-) is seen in the 15. Philip, P., and Drivsholm, A. A. G-banding analysis of complex aneuploidy in multiple myeloma bone marrow cells. Blood, 47: 69-77, 1976. majority of cases. Thus, careful cytogenetic analysis can pro- 16. Philip, P., Drivsholm, A., Hansen, N. E., Jensen, M. K., and Killman, S. A. vide information that contributes to the further characterization Chromosomes and survival in multiple myeloma. A banding study of 25 of malignant disorders of lymphoid cells. cases. Cancer Genet. Cytogenet., 2: 243-257, 1980. 17. Rowley, J. D. Abnormalities of chromosome no. 1 : significance in malignant transformation. Virchows Arch. B Cell Pathol., 29:139-144, 1978. ACKNOWLEDGMENTS 18. Rowley, J. D., and Fukuhara, S. Chromosome studies in non-Hodgkin lymphomas. Semin. Oncol., 7: 255-266, 1980. We are very grateful to Dr. Janet D. Rowley for critical review. 19. Rowley, J. D., Golomb, H. M., and Vardiman, J. Nonrandom chromosomal abnormalities in acute nonlymphocytic leukemia in patients treated for Hodgkin disease and non-Hodgkin lymphomas. Blood, 50: 759-770, 1977. REFERENCES 20. Sandberg, A. A. The leukemias: chronic granulocytic leukemia. Acute leukemias. The lymphomas. In: The Chromosomes in Human Cancer and 1. Anday, G. J., Fishkin, B., and Gabor, F. P. Cytogenetic studies in multiple Leukemia, pp. 183-412. Amsterdam: Elsevier/North Holland Biomedical myeloma. J. Natl. Cancer Inst., 52:1069-1079, 1974. Press, 1980. 2. Burk, K. H., Drewinko, B., Trujillo, J. M., and Ahearn, M. J. Establishment of 21. Seabright, M. A rapid banding technique for human chromosomes. Lancet, a human plasma cell line in vitro. Cancer Res., 38:2508-2513, 1978. 2:971-972, 1971. 3. Dartnell, J. A., Mundy, G. R., and Baikie, A. G. Cytogenetic studies in 22. Spriggs, A. I., Holt, J. M., and Bedford, J. Duplication of part of the long arm myeloma. Blood, 42: 229-239, 1973. of chromosome 1 in marrow cells of a treated case of myelomatosis. Blood, 4. Diehl, V., Schaadt, M., Kirchner, H., Hellriegel, K-P., Gudat, F., Fonatsch, 48: 595-599, 1976. C., Laskewitz, E., and Guggenheim, R. Long-term cultivation of plasma cells 23. Tassoni, E. M., Durant, J. R., Becker, S., and Kravits, B. Cytogenetic studies and autologous lymphoblasts (LCL) in vitro: a comparative study. Blut, 36: in multiple myeloma: a study of fourteen cases. Cancer Res., 27:806-810, 331-338, 1978. 1976. 5. Finan, J. B., Daniele, R. P., Rowland, S. T., Jr., and Nowell, P. C. Cytoge- 24. Uchiyama, T., Takatsuki, K., Uchino, H., Kotani, H., Yonezawa, T., and netics of chronic T cell leukemia: including two patients with a 14q+ Kitani, T. Non-secretory myeloma (in Japanese). Saisin Igaku, 33: 356-364, translocation. Virchows Arch. B Cell Pathol., 29:121-127, 1978. 1978. 6. Fukuhara, S., Shirakawa, S., and Uchino, H. Specific marker chromosome 25. Ueshima, Y., Fukuhara, S., Hattori, T., Uchiyama, T., Takatsuki, K., and 14 in malignant lymphomas. Nature (Lond.), 259:210-211, 1976. Ushino, H. Chromosome studies in adult T-cell leukemia in Japan: signifi- 7. Gahrton, G., and Robert, K.-H. Chromosomal aberrations in chronic B-cell cance of trisomy 7. Blood, 58: 420-425, 1981. lymphocytic leukemia. Cancer Genet. Cytogenet., 6:171-181, 1982. 26. Van Den Berghe, H., Louwagle, A., Broeckaert-Van Orshoven, A., David, 8. Gahrton, G., Zech, L., Nillsson, K., L6nnovist, B., and Carlstrom, A. Two G., Verwilghen, R., Michaux, L., and Sokal, G. Philadelphia chromosome in translocations, t(11 ;14) and t(1 ;6), in a patient with plasma cell leukaemia human multiple myeloma. J. Natl. Cancer Inst., 63:11-16, 1979. and 2 populations of plasma cells. Scand. J. Haematol., 24: 42-46, 1980. 27. Whang-Peng, J., Knutsen, T., O'Donnell, J. F., and Brereton, H. D. Acute 9. International System for Human Cytogenetic Nomenclature (1978). Cyto- non-lymphocytic leukemia and acute myeloproliferative syndrome following genet. Cell Genet., 21: 309-404, 1978. radiation therapy for non-Hodgkin's lymphoma and chronic lymphocytic 10. Jensen, M. K., Eriksen, J., and Djernes, B. W. Cytogenetic studies in leukemia. Cytogenetic studies. Cancer (Phila.), 44:1592-1600, 1979. myelomatosis. Scand. J. Haematol., 14:201-209, 1975. 28. Woodruff, R. K., Malpas, J. S., Paxton, A. M., and Lister, T. A. Plasma cell 11. Liang, W., Hopper, J. E., and Rowley, J. D. Karyotypic abnormalities and leukemia (PCL): a report on 15 patients. Blood, 52: 839-845, 1978. clinical aspects of patients with multiple myeloma and related paraprotei- 29. Wurster-Hill, D. H., Mclntvre, D. R., and Cornwell, G. G., III. Chromosome nemic disorders. Cancer (Phila.), 44: 630-644, 1979. studies in myelomatosis. Virchows Arch. B Cell Pathol., 29: 93-97, 1978.

FEBRUARY1983 909

'i,~i ~~iii~ 84~ii '~ ~ii~'~~i~i ~!~i ii;~ii~ ~i~i, ~ ~iiiiii i~!"~i~i~i:ii:;;/~

i~ ~ ~ ~ ~i~:~!~ iii~iii ~ ~ ~ ~i~i~i~i~~ ~?~ I~IIL~ ~'

...... :::: ;:;: :~::: ~..... 11 t(11;14)

Fig. 1. Partial karyotypes of G-banded (a) and Q-banded (b to d) cells illustrating some of the abnormalities in cells from Cases 1 (a), 4 (b), 6 (c), and 7 (d). A complete description of the karyotype is included in Table 2. /, der(17)t(1;17)(q12;p13); II, markers invoMng lq and unknown chromosomes; III, der(16)t(1 ;16)(ql 2;pl 3); IV, der(18)t(1 "18)(ql 2;pl 1 ).

Fig. 2. Q-banded karyotype of a cell from Case 2. The abnormal chromosomes t(6;8)(q13;pl 1 ), der(9)t(1 ;9)(lqter--~lql 2::1q44-*1q12::gq34--~9pter) and the missing Y chromosome and No. 13 are indicated with arrows.

910 CANCER RESEARCH VOL. 43

Fig. 3. Q-banded karyotype of a cell from Case 3. The abnormal chromosomes including a marker involving l q and an unknown chromosome, der(8)t(1 ;8)(1 qter--~cen-*8qter), der(9)t(1 ;9)(q21 ;p24), tier(10)t(1 ;10)(p31 ;q26), a missing X chromosome and missing Nos. 1 3 and 22 are indicated with arrows.

Fig. 4. Examples of abnormal cells from Case 5 at various stage of his disease, a, myeloma cells in the bone marrow aspirate at the time of diagnosis. May- Giemsa, x 1000. b, atypical plasmacytoid cells with convoluted nuclei in peripheral blood during the leukemic phase, x 400. c, myeloma cells in the pleural effusion before death, x 100.

FEBRUARY1983 911

Fig. 5. Q-banded karyotype of a cell from the pleural effusion in Case 5. The abnormal chromosomes 4q+, 6q-, der(8)t(8;15)(p23;q12), 14q+, der(16)t(1 ;16)(q21 ;pl 3), a missing No. 15, and missing No. 18 are indicated with arrows. The missing No. 13 is due to random loss of this chromosome.

912 CANCER RESEARCH VOL. 43

Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 1983 American Association for Cancer Research. Cytogenetic Studies and Clinical Aspects of Patients with Plasma Cell Leukemia and Leukemic Macroglobulinemia

Yoshimi Ueshima, Shirou Fukuhara, Kenichi Nagai, et al.

Cancer Res 1983;43:905-912.

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