96
ported by retrospective data of other investigators and our own cross-sectional and retrospective data. To determine whether the relationship of pulmonary dysfunction to lung cancer is
14q+
MARKER CHROMOSOME IN MULTIPLE MYELOMA AND PLASMA CELL LEUKAMIA
the temporal sequence of development must be examined. In a longitudinal, follow-up study we are trying to clarify the role of pulmonary impairment, the common familial component(s), and the cofactors, along with the natural history of C.O.P.D. and lung cancer. We hope that others will undertake similar studies. Only through such efforts can these complex interrelationships be understood and intervention and prevention procedures for both C.O.P.D. and lung cancer be made more rational.
aaiological,
Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205 U.S.A.
*24 h culture without phytohsemaggtutinin. no. 14 chromosomes
t7 metaphases showed that both 14q+ markers.
were
replaced by
BERNICE H. COHEN
support the proposal of McCaw et al.12 that genes on chromosome 14 are involved in the regulation of lymphoid cell
findings MARKER CHROMOSOMES IN MULTIPLE MYELOMA AND PLASMA-CELL LEUKÆMIA
14q+
SIR,-Various types of chromosomal abnormalities have been detected in the malignant cells of patients with lymphoproliferative disorders—e.g., Burkitt’s lymphoma,1-3 Hodgkin’s
disease,4and malignant lymphomas.s
An abnormal chromosome 14 with extra bands at the end of the long arm (14q+) has been observed very frequently. There are only two previous reports6·’ of this 14q+ marker in multiple myeloma (two patients) and plasma-cell leukaemia (1 patient). We have found a 14q+ marker chromosome in bone-marrow cells of three myeloma patients and in the peripheral blood leucocytes of one patient with plasma-cell leuksEmia, out of a total of twenty-two patients with myelomatosis. The chromosomes were analysed by quinacrine fluorescence.8 Patients 1 and 2 had IgG-kappa type myelomas and patient 3 an IgA-lambda type. All three patients had high concentrations of serum-paraproteins (7-92, 6.24, and 6-80 g/dl, respectively) when bone-marrow aspirates were taken for chromosome examination. Patient 4 had plasma-cell leukaemia with an IgA-kappa-type paraprotein level of 1.32 g/dl (about 5 times higher than normal). The cytogenetic data for these four patients (see table) showed that they all had a hyperdiploid clone in which the 14q+ marker had a high frequency. In the diploid cells both no. 14 chromosomes were normal. In some cells from patient 4, both no. 14 chromosomes were replaced by 14q+ markers. Patient 2 had trisomy 13 and trisomy 15, whereas patient 1 had trisomy 15 as well as the 14q+ markers. There were no changes in the total number of chromosomes in the D group of patients 3 and 4. The origin of the extra band at the end of the 14q+ markers could not be determined because of the complex nature of the chromosomal rearrangements.’ However, a translocation between chromosomes no. 11 and 14 (t[ll;14] [q23;q32]) was detected in patient 4. The clinical details and the complete chromosomal analysis for these patients will be reported elsewhere. The 14q+ chromosome is consistently present in various types of lymphoid cell malignancies but not in the myeloproliferative disorders. The assumption that 14q+ is a common cytogenetic marker in lymphoid disorders is supported by the high proportion of myeloma patients with a large acrocentric marker chromosome found by conventional methods.9-11 Our Manolov, G., Manolova, Y. Nature, 1972, 237, 33. Zech, L., Haglund, U., Nilsson, K., Klein G. Int. J. Cancer, 1976, 17, 47. McCaw, B., K., Epstein, A. L., Kaplan, H. S., Hecht, F. ibid. 1977, 19, 482. Fukuhara, S., Shirakawa, S., Uchino, H. Nature, 1976, 259, 210. Fleischman, E. W., Prigogina, E. L. Hum. Genet., 1977, 35, 269. Wurster-Hill, D. H., McIntyre, O. R., Cornwell III, G. G., Maurer, L. H. Lancet, 1973, ii, 1031. 7. Philip, P. Hereditas, 1975, 80, 155. 8. Rowley, J. D. Blood, 1976, 48, 1. 9. Tassoni, E. M., Durant, J. R., Becker, S., Kravitz, B. Cancer Res. 1967, 27, 1. 2. 3. 4. 5. 6.
806. 10. Itani, S.,
Hoshino, T., Kawasaki, S., Nakayama, S. Acta hæm. Jap. 1970, 33, 54. 11. Dartnall, J. A., Mundy, G. R., Baikie, A. G. Blood, 1973, 42, 229.
proliferation. We thank Dr John Hopper for patient’s samples. W.L. was a postdoctoral trainee supported by National Research Service Award T32, USPHS GM 7190. Franklin McLean Memorial Research and Department of Medicine,
Institute,
WEITZE LIANG JANET D. ROWLEY
University of Chicago, Chicago, Illinois 60637, U.S.A.
DUPLICATION OF PART OF CHROMOSOME NO. 1 IN MYELOPROLIFERATIVE DISEASES seen a patient with myelofibrosis transforminto acute ing myeloblastic leukaemia who had a duplication of the distal part of the long arm of chromosome no. 1 in bonemarrow cells.’ Fifteen patients with blood disorders who had either trisomy 1 or duplication of part of this chromosome in bone-marrow and/or abnormal blood-cells have- previously been described.2-9 In these patients, although the duplicated
SIR,-We have
of duplicated part of chromosome and/or abnormal blood-cells.
Length
no.
1 in bone-marrow
Only q23-25 (shadowed) is duplicated in all patients. part of chromosome
1 was of variable length, there was of the chromosome, q23-25 (see figure), only portion that was duplicated in all. The diagnosis in seven patients was polycythaemia vera, three had myelofibrosis either initially or one
12.
no.
small
B. K., Hecht, F., Harnden, D. Sci. U.S.A. 1975, 72, 2071.
McCaw,
G., Teplitz, R. L. Proc.
natn.
Acad.
Gahrton, G., Friberg, K., Lindsten, J., Zech, L. Hereditas (in the press). Nowell, P., Jensen, J., Gardner, F., Scott, M., Chaganti, R. S. K., German, J. Cancer, 1976, 38, 1873. 3. Oshimura, M., Hayata, I., Surabhi, K., Sandberg, A. ibid. p. 748. 4. Rowley, J. D. ibid. 1975, 36, 1148. 5. Rowley, J. D. Proc. natn. Acad. Sci. U.S.A. 1975, 72, 152. 6. Warburton, D., Bluming, A. Blood, 1973, 42, 799. 7. Westin, J., Wahlström, J., Swolin, B. Scand. J. Hæmat. 1976, 17, 183. 8. Wurster-Hill, D., and others. Sem. Hemat. 1976, 13, 13. 9. Yamada, K., Furusawa, S. Blood, 1976, 47, 679.
1. 2.
ported by retrospective data of other investigators and our own cross-sectional and retrospective data. To determine whether the relationship of pulmonary dysfunction to lung cancer is
14q+
MARKER CHROMOSOME IN MULTIPLE MYELOMA AND PLASMA CELL LEUKAMIA
the temporal sequence of development must be examined. In a longitudinal, follow-up study we are trying to clarify the role of pulmonary impairment, the common familial component(s), and the cofactors, along with the natural history of C.O.P.D. and lung cancer. We hope that others will undertake similar studies. Only through such efforts can these complex interrelationships be understood and intervention and prevention procedures for both C.O.P.D. and lung cancer be made more rational.
aaiological,
Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205 U.S.A.
*24 h culture without phytohsemaggtutinin. no. 14 chromosomes
t7 metaphases showed that both 14q+ markers.
were
replaced by
BERNICE H. COHEN
support the proposal of McCaw et al.12 that genes on chromosome 14 are involved in the regulation of lymphoid cell
findings MARKER CHROMOSOMES IN MULTIPLE MYELOMA AND PLASMA-CELL LEUKÆMIA
14q+
SIR,-Various types of chromosomal abnormalities have been detected in the malignant cells of patients with lymphoproliferative disorders—e.g., Burkitt’s lymphoma,1-3 Hodgkin’s
disease,4and malignant lymphomas.s
An abnormal chromosome 14 with extra bands at the end of the long arm (14q+) has been observed very frequently. There are only two previous reports6·’ of this 14q+ marker in multiple myeloma (two patients) and plasma-cell leukaemia (1 patient). We have found a 14q+ marker chromosome in bone-marrow cells of three myeloma patients and in the peripheral blood leucocytes of one patient with plasma-cell leuksEmia, out of a total of twenty-two patients with myelomatosis. The chromosomes were analysed by quinacrine fluorescence.8 Patients 1 and 2 had IgG-kappa type myelomas and patient 3 an IgA-lambda type. All three patients had high concentrations of serum-paraproteins (7-92, 6.24, and 6-80 g/dl, respectively) when bone-marrow aspirates were taken for chromosome examination. Patient 4 had plasma-cell leukaemia with an IgA-kappa-type paraprotein level of 1.32 g/dl (about 5 times higher than normal). The cytogenetic data for these four patients (see table) showed that they all had a hyperdiploid clone in which the 14q+ marker had a high frequency. In the diploid cells both no. 14 chromosomes were normal. In some cells from patient 4, both no. 14 chromosomes were replaced by 14q+ markers. Patient 2 had trisomy 13 and trisomy 15, whereas patient 1 had trisomy 15 as well as the 14q+ markers. There were no changes in the total number of chromosomes in the D group of patients 3 and 4. The origin of the extra band at the end of the 14q+ markers could not be determined because of the complex nature of the chromosomal rearrangements.’ However, a translocation between chromosomes no. 11 and 14 (t[ll;14] [q23;q32]) was detected in patient 4. The clinical details and the complete chromosomal analysis for these patients will be reported elsewhere. The 14q+ chromosome is consistently present in various types of lymphoid cell malignancies but not in the myeloproliferative disorders. The assumption that 14q+ is a common cytogenetic marker in lymphoid disorders is supported by the high proportion of myeloma patients with a large acrocentric marker chromosome found by conventional methods.9-11 Our Manolov, G., Manolova, Y. Nature, 1972, 237, 33. Zech, L., Haglund, U., Nilsson, K., Klein G. Int. J. Cancer, 1976, 17, 47. McCaw, B., K., Epstein, A. L., Kaplan, H. S., Hecht, F. ibid. 1977, 19, 482. Fukuhara, S., Shirakawa, S., Uchino, H. Nature, 1976, 259, 210. Fleischman, E. W., Prigogina, E. L. Hum. Genet., 1977, 35, 269. Wurster-Hill, D. H., McIntyre, O. R., Cornwell III, G. G., Maurer, L. H. Lancet, 1973, ii, 1031. 7. Philip, P. Hereditas, 1975, 80, 155. 8. Rowley, J. D. Blood, 1976, 48, 1. 9. Tassoni, E. M., Durant, J. R., Becker, S., Kravitz, B. Cancer Res. 1967, 27, 1. 2. 3. 4. 5. 6.
806. 10. Itani, S.,
Hoshino, T., Kawasaki, S., Nakayama, S. Acta hæm. Jap. 1970, 33, 54. 11. Dartnall, J. A., Mundy, G. R., Baikie, A. G. Blood, 1973, 42, 229.
proliferation. We thank Dr John Hopper for patient’s samples. W.L. was a postdoctoral trainee supported by National Research Service Award T32, USPHS GM 7190. Franklin McLean Memorial Research and Department of Medicine,
Institute,
WEITZE LIANG JANET D. ROWLEY
University of Chicago, Chicago, Illinois 60637, U.S.A.
DUPLICATION OF PART OF CHROMOSOME NO. 1 IN MYELOPROLIFERATIVE DISEASES seen a patient with myelofibrosis transforminto acute ing myeloblastic leukaemia who had a duplication of the distal part of the long arm of chromosome no. 1 in bonemarrow cells.’ Fifteen patients with blood disorders who had either trisomy 1 or duplication of part of this chromosome in bone-marrow and/or abnormal blood-cells have- previously been described.2-9 In these patients, although the duplicated
SIR,-We have
of duplicated part of chromosome and/or abnormal blood-cells.
Length
no.
1 in bone-marrow
Only q23-25 (shadowed) is duplicated in all patients. part of chromosome
1 was of variable length, there was of the chromosome, q23-25 (see figure), only portion that was duplicated in all. The diagnosis in seven patients was polycythaemia vera, three had myelofibrosis either initially or one
12.
no.
small
B. K., Hecht, F., Harnden, D. Sci. U.S.A. 1975, 72, 2071.
McCaw,
G., Teplitz, R. L. Proc.
natn.
Acad.
Gahrton, G., Friberg, K., Lindsten, J., Zech, L. Hereditas (in the press). Nowell, P., Jensen, J., Gardner, F., Scott, M., Chaganti, R. S. K., German, J. Cancer, 1976, 38, 1873. 3. Oshimura, M., Hayata, I., Surabhi, K., Sandberg, A. ibid. p. 748. 4. Rowley, J. D. ibid. 1975, 36, 1148. 5. Rowley, J. D. Proc. natn. Acad. Sci. U.S.A. 1975, 72, 152. 6. Warburton, D., Bluming, A. Blood, 1973, 42, 799. 7. Westin, J., Wahlström, J., Swolin, B. Scand. J. Hæmat. 1976, 17, 183. 8. Wurster-Hill, D., and others. Sem. Hemat. 1976, 13, 13. 9. Yamada, K., Furusawa, S. Blood, 1976, 47, 679.
1. 2.
