Complex Karyotype Including Trisomy 8 in a Case of B-Chronic Lymphocytic Leukemia
The varying length of survival in B-cell chronic l y m p h o cytic l e u k e m i a (CLL) has led to d e v e l o p m e n t of different staging systems based on clinical and hematologic parameters [1]. As for other malignancies, c h r o m o s o m e studies have been performed to test the putative prognostic significance of the c h r o m o s o m a l abnormalities observed in CLL [2-4]. During the last decade, the number of CLL patients s t u d i e d reached 1,000 [4], but only 390 have been reported as having c h r o m o s o m a l aberrations [5]. Trisomy 12 is the most frequently reported c h r o m o s o m e abnormality, occurring in more than one third of CLL patients with clonal c h r o m o s o m a l aberrations [4}, followed by occurrence of a 1 4 q + marker, present in about 25% of cytogenetically abnormal patients. Our patient was a 66-year-old white man with no past m e d i c a l history and no exposure to radiation, chemotoxic drugs, or other mutagenic agents. On a d m i s s i o n in January 1991, the c o m p l e t e blood count (CBC) s h o w e d leukocytes 37,400/ml with a differential of l y m p h o c y t e s 90%, neutrophils 10%, a h e m o g l o b i n level of 14.8 g/dl, and a platelet count of 159,000/ml. I m m u n o p h e n o t y p e was positive for
Figure 1
the following markers: CD2 (11%), CD19 (88%), CD5 (99%), and sIg (95%), and bone m a r r o w (BM) b i o p s y s h o w e d an interstitial l y m p h o i d infiltration. A c c o r d i n g to the data, a diagnosis of B-CLL stage 0 of Rai classification was made. We used the same BM sample to establish three different cultures: one with a T-cell mitogen (phytohemaglutinin), one with a B-cell mitogen (pokeweed), and one without mitogens. Cytogenic analysis of both B - c e l l - s t i m u l a t e d and u n s t i m u l a t e d cultures s h o w e d n o r m a l m e t a p h a s e s (30 of 50) and metaphases with the following karyotype: 46,XY. -2,+8,der(16)t(2;16)(q21;q22). Cells from the T - c e l l stimulated culture s h o w e d only normal metaphases. A metaphase spread and a partial k a r y o t y p e of the case with the rearranged c h r o m o s o m e s is s h o w n in Figure 1. An exhaustive review of all karyotypes described in the fourth edition of the Catalog of Chromosome Aberrations in Cancer [5] s h o w e d no case with the same aberrations as those of our patient. A selective analysis of the trisomy 8-CLL-associated cases from the Catalog shows that this anomaly is more c o m m o n in B-CLL and always appears in h y p e r d i p l o i d karyotypes and as part of a c o m p l e x karyo-
Metaphase spread and partial karyotype of the case showing the rearranged chromosomes.
8
2
108 Cancer Genet Cytogenet 62:108-109 (1992) 0165-4608/92/$05.00
der (16) t(2;16)
© 1992 Elsevier Science Publishing Co., lnc, 655 Avenue of the Americas, New York. NY 10010
C o m p l e x Karyotype in CLL
type. Reported alterations of 2q21 and 16q22 in patients with CLL are very rare and appear in very c o m p l e x karyotypes. The n o n r e c u r r e n c e of these c h r o m o s o m a l changes makes their prognostic significance uncertain. However, the p u b l i s h e d data clearly show that a karyotype with abnormalities correlates with a poor prognosis [1-4]. Moreover, that c o m p l e x karyotypes carry a poorer prognosis as c o m p a r e d with single aberrations is probably true and might be significant w h e n larger studies are available [4]. On the other hand, cytogenetic analysis of the BM from the patient also s h o w e d 60% of normal metaphases. As other investigators suggest [2, 4], the presence of normal cells may be a reflection of residual n o n m a l i g n a n t cells, w h i c h is beneficial for the patient and m a y be the cause of the n o n a p p a r e n t aggressiveness of this case. A n o t h e r interesting finding is that our patient showed the a b o v e m e n t i o n e d alterations in cells from both unstimulated and B - c e l l - s t i m u l a t e d cultures, indicating that the mutational event had probably occurred at an undifferentiated progenitor in the BM that later became a B - l y m p h o i d cell. This work was supported by a grant from the Spanish Ministry of Science.
109
JUAN CRUZ CIGUDOSA MARIA JOSE CALASANZ ARTURO GULLON MARIA TERESA ARDANAZ
D e p a r t m e n t of Genetics University of Navarra Pamplona, Spain Department of Hematology Hospital Txagorritxu Vitoria, Spain
REFERENCES
1. Geisler C, Hansen MM (1989): B cell chronic lymphocytic leukaemia: Recent concepts in classification and treatment. Eur J Haematol 48(suppl 48):31-37. 2. Juliusson G, Robert K-H, Ost A, Friberg K, Beberfeld P, Nilsson B, Zech L, Gahrton G (1985): Prognostic information from cytogenetic analysis in chronic B-lymphocytic leukemia and leukemic immunocytoma. Blood 65:134-141. 3. Gahrton G, luliusson G (1988): Clinical implication of chromosomal aberrations in chronic B-lymphocytic leukemia cells. Nouv Rev Fr Hematol 30:389-392. 4. Juliusson G, Gahrton G (1990): Chromosome aberrations in Bcell chronic lymphocytic leukemia. Pathogenic and clinical implications. Cancer Genet Cytogenet 45:143-160. 5. Mitelman F (1991): Catalog of Chromosome Aberrations in Cancer, 4th Ed. Wiley-Liss. New York.
The varying length of survival in B-cell chronic l y m p h o cytic l e u k e m i a (CLL) has led to d e v e l o p m e n t of different staging systems based on clinical and hematologic parameters [1]. As for other malignancies, c h r o m o s o m e studies have been performed to test the putative prognostic significance of the c h r o m o s o m a l abnormalities observed in CLL [2-4]. During the last decade, the number of CLL patients s t u d i e d reached 1,000 [4], but only 390 have been reported as having c h r o m o s o m a l aberrations [5]. Trisomy 12 is the most frequently reported c h r o m o s o m e abnormality, occurring in more than one third of CLL patients with clonal c h r o m o s o m a l aberrations [4}, followed by occurrence of a 1 4 q + marker, present in about 25% of cytogenetically abnormal patients. Our patient was a 66-year-old white man with no past m e d i c a l history and no exposure to radiation, chemotoxic drugs, or other mutagenic agents. On a d m i s s i o n in January 1991, the c o m p l e t e blood count (CBC) s h o w e d leukocytes 37,400/ml with a differential of l y m p h o c y t e s 90%, neutrophils 10%, a h e m o g l o b i n level of 14.8 g/dl, and a platelet count of 159,000/ml. I m m u n o p h e n o t y p e was positive for
Figure 1
the following markers: CD2 (11%), CD19 (88%), CD5 (99%), and sIg (95%), and bone m a r r o w (BM) b i o p s y s h o w e d an interstitial l y m p h o i d infiltration. A c c o r d i n g to the data, a diagnosis of B-CLL stage 0 of Rai classification was made. We used the same BM sample to establish three different cultures: one with a T-cell mitogen (phytohemaglutinin), one with a B-cell mitogen (pokeweed), and one without mitogens. Cytogenic analysis of both B - c e l l - s t i m u l a t e d and u n s t i m u l a t e d cultures s h o w e d n o r m a l m e t a p h a s e s (30 of 50) and metaphases with the following karyotype: 46,XY. -2,+8,der(16)t(2;16)(q21;q22). Cells from the T - c e l l stimulated culture s h o w e d only normal metaphases. A metaphase spread and a partial k a r y o t y p e of the case with the rearranged c h r o m o s o m e s is s h o w n in Figure 1. An exhaustive review of all karyotypes described in the fourth edition of the Catalog of Chromosome Aberrations in Cancer [5] s h o w e d no case with the same aberrations as those of our patient. A selective analysis of the trisomy 8-CLL-associated cases from the Catalog shows that this anomaly is more c o m m o n in B-CLL and always appears in h y p e r d i p l o i d karyotypes and as part of a c o m p l e x karyo-
Metaphase spread and partial karyotype of the case showing the rearranged chromosomes.
8
2
108 Cancer Genet Cytogenet 62:108-109 (1992) 0165-4608/92/$05.00
der (16) t(2;16)
© 1992 Elsevier Science Publishing Co., lnc, 655 Avenue of the Americas, New York. NY 10010
C o m p l e x Karyotype in CLL
type. Reported alterations of 2q21 and 16q22 in patients with CLL are very rare and appear in very c o m p l e x karyotypes. The n o n r e c u r r e n c e of these c h r o m o s o m a l changes makes their prognostic significance uncertain. However, the p u b l i s h e d data clearly show that a karyotype with abnormalities correlates with a poor prognosis [1-4]. Moreover, that c o m p l e x karyotypes carry a poorer prognosis as c o m p a r e d with single aberrations is probably true and might be significant w h e n larger studies are available [4]. On the other hand, cytogenetic analysis of the BM from the patient also s h o w e d 60% of normal metaphases. As other investigators suggest [2, 4], the presence of normal cells may be a reflection of residual n o n m a l i g n a n t cells, w h i c h is beneficial for the patient and m a y be the cause of the n o n a p p a r e n t aggressiveness of this case. A n o t h e r interesting finding is that our patient showed the a b o v e m e n t i o n e d alterations in cells from both unstimulated and B - c e l l - s t i m u l a t e d cultures, indicating that the mutational event had probably occurred at an undifferentiated progenitor in the BM that later became a B - l y m p h o i d cell. This work was supported by a grant from the Spanish Ministry of Science.
109
JUAN CRUZ CIGUDOSA MARIA JOSE CALASANZ ARTURO GULLON MARIA TERESA ARDANAZ
D e p a r t m e n t of Genetics University of Navarra Pamplona, Spain Department of Hematology Hospital Txagorritxu Vitoria, Spain
REFERENCES
1. Geisler C, Hansen MM (1989): B cell chronic lymphocytic leukaemia: Recent concepts in classification and treatment. Eur J Haematol 48(suppl 48):31-37. 2. Juliusson G, Robert K-H, Ost A, Friberg K, Beberfeld P, Nilsson B, Zech L, Gahrton G (1985): Prognostic information from cytogenetic analysis in chronic B-lymphocytic leukemia and leukemic immunocytoma. Blood 65:134-141. 3. Gahrton G, luliusson G (1988): Clinical implication of chromosomal aberrations in chronic B-lymphocytic leukemia cells. Nouv Rev Fr Hematol 30:389-392. 4. Juliusson G, Gahrton G (1990): Chromosome aberrations in Bcell chronic lymphocytic leukemia. Pathogenic and clinical implications. Cancer Genet Cytogenet 45:143-160. 5. Mitelman F (1991): Catalog of Chromosome Aberrations in Cancer, 4th Ed. Wiley-Liss. New York.
