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A translocation between 3q21 and 12q24 in a patient with minimally differentiated acute myeloid leukemia (AML-MO)
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A Translocation between 3q21 and 12q24 in a Patient with Minimally Differentiated Acute Myeloid Leukemia (AML-MO) Noboru Yamagata, Chihiro Shimazaki, Takehisa Kikuta, Hideyo Hirai, Toshiya Sumikuma, Yoshikazu Sudo, Eishi Ashihara, Hideo Goto, Tohru Inaba, Naohisa Fujita, and Masao Nakagawa ABSTRACT: Only a small number of reports have described the cytogenetic analysis of minimally differentiated acute myeloid leukemia (AML, MO). We performed a cytogenetic analysis on a patient with AML (MO) with a normal platelet count. It revealed a chromosomal translocation between chromosome bands 3q21 and 12q24.3q. Abnormalities in AML are known to be associated with normal or elevated platelet counts. 3q21 and 12q24 are common translocation sites & AML patients, but this is the first report of translocation t(3;12)(q21;q24) in an AML patient. @ Elsevier Science Inc., 1997
INTRODUCTION A small number of reports have described the cytogenetic analysis of minimally differentiated acute myeloid leukemia (AML-M0 in the French-American-British classification) [1-3]. 3q abnormalities in AML are associated with normal or elevated platelet counts and abnormal megakaryopoiesis. 3q21 and/or 3q26 may be the site responsible for this unique clinical feature [4-6]. In this report, we describe a patient with AML (M0) who had a normal platelet count and a chromosomal translocation between chromosome bands 3q21 and 12q24. CASE REPORT
A 52-year-old man was referred to our hospital because of easy fatigability in December 1995. His physical examination was unremarkable, with no lymphadenopathy or splenomegaly. Laboratory data were as follows: hemoglobin 6.0 g/dL; white blood cells (WBC) 2.0 x 109/L with 32% blasts, 44% lymphocytes, 1% monocytes, and 23% neutrophils; and platelets 371 x 109/L. An excessive variation was seen in the size of platelets. A bone marrow examination revealed a normocellular marrow with 60.4% blasts (Figure 1). The leukemic cells had no Auer rods, a high
From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku, Kyoto 602, Japan. Address reprint requests to: Dr. Noboru Yamagata, Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku, Kyoto 602, Japan. Received June 14, 1996; accepted September 23, 1996. Cancer Genet Cytogenet 9 7 : 9 0 - 9 3 (1997) @ Elsevier Science Inc., 1997 655 Avenue of the Americas, N e w York, NY 10010
nuclear/cytoplasmic ratio, and were negative for myeloperoxidase and Sudan black-B staining. Flow cytometric analysis showed that blasts were positive for CD13, CD33, CD34, and HLA-DR, but negative for CD2, cytoplasmic CD3, CD4, CD5, CD7, CD8, CD10, CD14, CD15, CD19, CD20, cytoplasmic CD22, CD41a, CD41b, CD42a, and CD42b. The patient was diagnosed as having AML (M0) according to the FAB classification [7]. He was treated first with idarubicin and cytosine arabinoside with no response. A second induction therapy consisting of behenoyl-arabinofuranosyl cytosine (BHAC), daunorubicin, 6-mercaptopurine (6-MP), and VP-16 was effective, resulting in a partial remission. He suffered from lung and liver abscess during his WBC nadir and now is being treated with a combination of antibiotics. CYTOGENETIC FINDINGS
Cytogenetic examination was performed on his admission in December 1995. The bone marrow ceils were cultured for 24 hours without mitogens. Two hours before the cells were harvested, ethidium bromide was added to the culture at a final concentration 10 ~g/mL [8]. Metaphase cells were collected by adding Colcemid 15 min before fixation. Chromosome preparations were made by the ordinary airdrying method. The trypsin-Giemsa method was performed for G-banding. Chromosome identification and karyotype designation were made according to the ISCN nomenclature [9]. Four out of five metaphase cells analyzed showed a reciprocal translocation between the long arm of chromosome 3 and the long arm of chromosome 12, t(3;12)(q21;q24) (Figure 2).
0165-4608/97/$17.00 PII S0165-4608(96)00339-1
t(3;12)(q21;q24) in (AML-M0)
91
Figure 1
Leukemiccells in bone marrow observed at diagnosis.
DISCUSSION
Some reports have described cytogenetic abnormalities in M0 patients [1-3]. The patients with M0 in these reports have relatively complex chromosomal abnormalities. Abnormalities of chromosomes 5, 7, 8, and 13 are frequently seen in these patients. However, no consistent chromosomal abnormality has been reported in MtI patients. 3q21 and 12q24 are common translocation sites in AML blasts. In patients with M0, abnormalities of chromosomes 3 or 12 are sometimes seen [1-3]. However, t o our knowledge, this is the first reported case of a reciprocal translocation between these sites in AML. AML patients with 3q abnormalities have been reported to have unique clinical manifestations, involving thrombopoiesis, such as normal or elevated platelet counts, and hyperplasia or dysplasia of megakaryocytes. 3q21 and/or 3q26 may be the responsible site of this unique clinical feature ~¢--6, 10]. Recently, a thrombopoietin (TPO)-encoding lesion was localized to 3q26-q27. However, overexpression of the TPO gene has not been detected in patients with the 3q21q26 syndrome [11, 12], suggesting that overproduction of TPO is not a cause of this syndrome. Some unknown mechanism of platelet production might be associated with 3q. Cigudosa et al. have reported two cases of t(3;11)(q21;q13) without abnormal megakaryopo~es~s I13L They have suggested that the clinical features of the 3q21q26 s3md~ome might be restricted either to the breakpoint of 3q26 to the simultaneous involvement of 3q21 and 3q26 [13]. However several cases with 3q21 abnormality without 3q26 abnormality havebeen reported to have relatively normal or high platelet count with megakaryocytic dysplasia [5, 6]. These cases together with our case, may suggest a possible relationship between
3q21 and thrombopoiesis. The difference of clinical features between t(3;11)(q21;q13) and t(3;12)(q21;q24) may be due to the different 3q21 translocation sites in these patients or to functional differences between 11q13 and 12q24. Several genes, such as transferrin [14], zinc finger protein 9 [15], the retinol-binding protein 1 [16], and nuclear protein BM28 [17] are localized to 3q21. Several important genes for DNA replication and cell division are localized to 12q24 as well. They include genes-encoding transcription factors and cytokines such as zinc finger protein 10 [18], zinc finger protein 26 [19], transcription factor I [20], replication factor C5 [21], polymerase ~ [22], and interferon ~/ [23]. The abnormal expression of genes encoded in 3q21 and 12q24 may play an important role in the unique clinical manifestations of this patient. Further analysis of 3q abnormalities is warranted to clarify the mechanisms of thrombopoiesis and oncogenesis in AML (M0).
REFERENCES
1. Lee EJ, Pollak A, Leavitt RD, Testa JR, Schiffer CA (1987): Minimally differentiated acute nonlymphocytic leukemia: A distinct entity. Blood 70:1400-1406. 2. Venditti A, Del Poeta G, Stasi R, Masi M, Bruno A, Buccisano F, Cox C, Coppetelli U, Aronica G, Simone MD, Papa G, Tribalto M, Amadori S (1994): Minimally differentiated acute myeloid leukaemia (AML-MO): Cytochemical, immunophenotypic and cytogenetic analysis of 19 cases. Br J Haematol 88:784-793. 3. Cuneo A, Ferrant A, Michanx JL, Boogaerts M, Demuynck H, Van Orshoven A, Criel A, Stul M, Dal Cin P, Hernanndez J, Chatelain B, Doyen C, Louwagie A, Castoldi G, Cassiman JJ, Van Den Berghe H (1995): Cytogenetic profile of minimally differentiated (FAB M0) acute myeloid leukemia: Correlation with clinicobiologic findings. Blood 85:3688-3694. 4. Bitter MA, Neilly ME, Le Beau MM, Pearson MG, Rowley JD
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N. Yamagata et al.
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F i g u r e 2 Karyotype at diagnosis showing t(3;]2)(q21;q24). Arrows indicate rearranged chromosomes at the breakpoints.
(1985): Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia. Blood 66: 1362-1370.
5. Bloomfield CD, Garson OM, Volin L, Knuutila S, de la Chapelle A (1985): t(1;3)(p36;q21) in acute nanlymphocytic leukemia: A new cytogenetic-clinicopathologic association. Blood 66:1409-1413. 6. Grigg AP, Gascoyne RD, Phillips GL, Horsman DE (1993): Clinical, haematological and cytogenetic features in 24 patients with structural rearrangements of the Q arm of chromosome 3. Br J Haemato] 83:158-165. 7. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1991): Proposals for the recognition of minimally differentiated acute myeloid leukaemia. Br J Haematol 78:325-329. 8. Misawa S, Horiike S, Taniwaki J, Abe T, Takino T (1986): Prefixation treatment with ethidium bromide for high resoln-
tion banding analysis of chromosomes from cultured human bone marrow cells. Cancer Genet Cytogenet 22:319-329. 9. ISCN (1985): An International System for Human Cytogenetic Nomenclature. DG Harden and HP Klinger, eds. Karger, Basel. 10. Bellomo MJ, Parlier V, M~ihlematter D, Grob JP, Beris PH (1992): Three new cases of chromosome 3 rearrangement in bands q21 and q26 with abnormal thrombopoiesis bring further evidence to the existence of a 3q21q26 syndrome. Cancer Genet Cytogenet 59:138-160. 11. Suzukawa K, Satoh H, Taniwaki M, Yokota J, Morishita K (1995): The human thrombopoietin gene is located on chromosome 3q26.33-q27, but is not transcriptionally activated in leukemia cells with 3q21 and 3q26 abnormalities (3q21q26 syndrome). Leukemia 9:1328-1331. 12. Bouscary D, Fontenay-Roupie M, Chretien S, Hardy AC, Vigui6 F, Picard F, Melle J, Dreyfus F (1995): Thrombopoietin is not responsible for the thrombocytosis observed in
t(3;12)(q21;q24) in (AML-M0)
13.
14.
15.
16.
17.
18.
patients with acute myeloid leukemias and the 3q21q26 syndrome. Br J Haematol 91:425-427. Cigudosa JC, Calasanz MJ, Odero MD, Marin J. Bengoechea E, Gulldn A (1995): A recurrent translocation, t(3;11)(q21;q13), found in two distinct cases of acute myeloid leukemia. Cancer Genet Cytogenet 83:119-120. Yang F, Lure JB, McGill JR, Moore CM, Naylor SL, van Bragt PH, Baldwin WD, Bowman BH (1984): Human transferrin: cDNA characterization and chromosomal localization. Proc Natl Acad Sci USA 81:2752-2756. Lnsis AI, Rajavachisth TB, Klisak I, Heinzmann C, Mohandas T, Sparkes RS (1990): Mapping of the gene for CNBP, a finger protein, to human chromosome 3q13.3-q24. Genomics 8: 411--414. Nilsson MH, Spurr NK, Lundvall J, Rask L. Peterson PA (1988): Human cellular retinol-binding protein gene organization and chromosomal location. Eur J Biochem 173:35-44. Todorov I, Lavigne J, Sakr F, Kaneva R, Folsy S, Bibor-Hardy V (1991): Nuclear matrix protein mitotin mRNA is expressed at constant level during the cell cycle. Biochem Biophys Res Commun 177:395-400. Rousseau-Merck MF, Hillion J, Jonveaux P, Couillin P, Seit6 P, Thiesen HJ, Berger R (1993): Chromosomal localization of 9 KOX zinc finger genes: Physical linkage suggests clustering of KOX genes on chromosomes 12, 16, and 19. Hum Genet 92:583-587.
93
19. Huebner K, Druck T, Croce CM, Thiesen HJ (1991): Twentyseven nonover|apping zinc finger cDNAs from human T cells map to nine different chromosomes with apparent clustering. Am J Hum Genet 48:726-740. 20. Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J (1992): Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF). Genomics 13:293300. 21. Okumura K, Nogami M, Taguchi H, Dean FB, Chen M, Pan ZQ, Hurwitz J, Shiratori A, Murakami Y, Ozawa K, Eki T (1995): Assignment of the 36.5-kDa (RFC5), 37-kDa (RFC4), 38-kDa (RFC3), and 40-kDa (RFC2) subunit genes of human replication factor C to chromosome bands 12q24.2-q24.3, 3q27, 13q12.3-q13, and 7q11.23. Genomics 25:274-278. 22. Szpier J, Pedeutour F, Kesti T, Riviere M, Syvfioja JE, TurcCarel C, Szpirer C (1994): Localization of gene for DNA polymerase e (POLE) to human chromosome 12q24.3 and rat chromosome 12 by somatic cell hybrid panels and fluorescence in situ hybridization. Genomics 20:223-226. 23. Trent JM, Olson S, Lawn RM (1982): Chromosomal localization of human leukocyte, fibroblast, and immune interferon genes by means of in situ hybridization. Proc Natl Acad Sci USA 79:7809-7813.
A Translocation between 3q21 and 12q24 in a Patient with Minimally Differentiated Acute Myeloid Leukemia (AML-MO) Noboru Yamagata, Chihiro Shimazaki, Takehisa Kikuta, Hideyo Hirai, Toshiya Sumikuma, Yoshikazu Sudo, Eishi Ashihara, Hideo Goto, Tohru Inaba, Naohisa Fujita, and Masao Nakagawa ABSTRACT: Only a small number of reports have described the cytogenetic analysis of minimally differentiated acute myeloid leukemia (AML, MO). We performed a cytogenetic analysis on a patient with AML (MO) with a normal platelet count. It revealed a chromosomal translocation between chromosome bands 3q21 and 12q24.3q. Abnormalities in AML are known to be associated with normal or elevated platelet counts. 3q21 and 12q24 are common translocation sites & AML patients, but this is the first report of translocation t(3;12)(q21;q24) in an AML patient. @ Elsevier Science Inc., 1997
INTRODUCTION A small number of reports have described the cytogenetic analysis of minimally differentiated acute myeloid leukemia (AML-M0 in the French-American-British classification) [1-3]. 3q abnormalities in AML are associated with normal or elevated platelet counts and abnormal megakaryopoiesis. 3q21 and/or 3q26 may be the site responsible for this unique clinical feature [4-6]. In this report, we describe a patient with AML (M0) who had a normal platelet count and a chromosomal translocation between chromosome bands 3q21 and 12q24. CASE REPORT
A 52-year-old man was referred to our hospital because of easy fatigability in December 1995. His physical examination was unremarkable, with no lymphadenopathy or splenomegaly. Laboratory data were as follows: hemoglobin 6.0 g/dL; white blood cells (WBC) 2.0 x 109/L with 32% blasts, 44% lymphocytes, 1% monocytes, and 23% neutrophils; and platelets 371 x 109/L. An excessive variation was seen in the size of platelets. A bone marrow examination revealed a normocellular marrow with 60.4% blasts (Figure 1). The leukemic cells had no Auer rods, a high
From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku, Kyoto 602, Japan. Address reprint requests to: Dr. Noboru Yamagata, Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku, Kyoto 602, Japan. Received June 14, 1996; accepted September 23, 1996. Cancer Genet Cytogenet 9 7 : 9 0 - 9 3 (1997) @ Elsevier Science Inc., 1997 655 Avenue of the Americas, N e w York, NY 10010
nuclear/cytoplasmic ratio, and were negative for myeloperoxidase and Sudan black-B staining. Flow cytometric analysis showed that blasts were positive for CD13, CD33, CD34, and HLA-DR, but negative for CD2, cytoplasmic CD3, CD4, CD5, CD7, CD8, CD10, CD14, CD15, CD19, CD20, cytoplasmic CD22, CD41a, CD41b, CD42a, and CD42b. The patient was diagnosed as having AML (M0) according to the FAB classification [7]. He was treated first with idarubicin and cytosine arabinoside with no response. A second induction therapy consisting of behenoyl-arabinofuranosyl cytosine (BHAC), daunorubicin, 6-mercaptopurine (6-MP), and VP-16 was effective, resulting in a partial remission. He suffered from lung and liver abscess during his WBC nadir and now is being treated with a combination of antibiotics. CYTOGENETIC FINDINGS
Cytogenetic examination was performed on his admission in December 1995. The bone marrow ceils were cultured for 24 hours without mitogens. Two hours before the cells were harvested, ethidium bromide was added to the culture at a final concentration 10 ~g/mL [8]. Metaphase cells were collected by adding Colcemid 15 min before fixation. Chromosome preparations were made by the ordinary airdrying method. The trypsin-Giemsa method was performed for G-banding. Chromosome identification and karyotype designation were made according to the ISCN nomenclature [9]. Four out of five metaphase cells analyzed showed a reciprocal translocation between the long arm of chromosome 3 and the long arm of chromosome 12, t(3;12)(q21;q24) (Figure 2).
0165-4608/97/$17.00 PII S0165-4608(96)00339-1
t(3;12)(q21;q24) in (AML-M0)
91
Figure 1
Leukemiccells in bone marrow observed at diagnosis.
DISCUSSION
Some reports have described cytogenetic abnormalities in M0 patients [1-3]. The patients with M0 in these reports have relatively complex chromosomal abnormalities. Abnormalities of chromosomes 5, 7, 8, and 13 are frequently seen in these patients. However, no consistent chromosomal abnormality has been reported in MtI patients. 3q21 and 12q24 are common translocation sites in AML blasts. In patients with M0, abnormalities of chromosomes 3 or 12 are sometimes seen [1-3]. However, t o our knowledge, this is the first reported case of a reciprocal translocation between these sites in AML. AML patients with 3q abnormalities have been reported to have unique clinical manifestations, involving thrombopoiesis, such as normal or elevated platelet counts, and hyperplasia or dysplasia of megakaryocytes. 3q21 and/or 3q26 may be the responsible site of this unique clinical feature ~¢--6, 10]. Recently, a thrombopoietin (TPO)-encoding lesion was localized to 3q26-q27. However, overexpression of the TPO gene has not been detected in patients with the 3q21q26 syndrome [11, 12], suggesting that overproduction of TPO is not a cause of this syndrome. Some unknown mechanism of platelet production might be associated with 3q. Cigudosa et al. have reported two cases of t(3;11)(q21;q13) without abnormal megakaryopo~es~s I13L They have suggested that the clinical features of the 3q21q26 s3md~ome might be restricted either to the breakpoint of 3q26 to the simultaneous involvement of 3q21 and 3q26 [13]. However several cases with 3q21 abnormality without 3q26 abnormality havebeen reported to have relatively normal or high platelet count with megakaryocytic dysplasia [5, 6]. These cases together with our case, may suggest a possible relationship between
3q21 and thrombopoiesis. The difference of clinical features between t(3;11)(q21;q13) and t(3;12)(q21;q24) may be due to the different 3q21 translocation sites in these patients or to functional differences between 11q13 and 12q24. Several genes, such as transferrin [14], zinc finger protein 9 [15], the retinol-binding protein 1 [16], and nuclear protein BM28 [17] are localized to 3q21. Several important genes for DNA replication and cell division are localized to 12q24 as well. They include genes-encoding transcription factors and cytokines such as zinc finger protein 10 [18], zinc finger protein 26 [19], transcription factor I [20], replication factor C5 [21], polymerase ~ [22], and interferon ~/ [23]. The abnormal expression of genes encoded in 3q21 and 12q24 may play an important role in the unique clinical manifestations of this patient. Further analysis of 3q abnormalities is warranted to clarify the mechanisms of thrombopoiesis and oncogenesis in AML (M0).
REFERENCES
1. Lee EJ, Pollak A, Leavitt RD, Testa JR, Schiffer CA (1987): Minimally differentiated acute nonlymphocytic leukemia: A distinct entity. Blood 70:1400-1406. 2. Venditti A, Del Poeta G, Stasi R, Masi M, Bruno A, Buccisano F, Cox C, Coppetelli U, Aronica G, Simone MD, Papa G, Tribalto M, Amadori S (1994): Minimally differentiated acute myeloid leukaemia (AML-MO): Cytochemical, immunophenotypic and cytogenetic analysis of 19 cases. Br J Haematol 88:784-793. 3. Cuneo A, Ferrant A, Michanx JL, Boogaerts M, Demuynck H, Van Orshoven A, Criel A, Stul M, Dal Cin P, Hernanndez J, Chatelain B, Doyen C, Louwagie A, Castoldi G, Cassiman JJ, Van Den Berghe H (1995): Cytogenetic profile of minimally differentiated (FAB M0) acute myeloid leukemia: Correlation with clinicobiologic findings. Blood 85:3688-3694. 4. Bitter MA, Neilly ME, Le Beau MM, Pearson MG, Rowley JD
92
N. Yamagata et al.
I
3
2
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7
8
13
14
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20
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22
5
10
11
16
17
18
X
Y
F i g u r e 2 Karyotype at diagnosis showing t(3;]2)(q21;q24). Arrows indicate rearranged chromosomes at the breakpoints.
(1985): Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia. Blood 66: 1362-1370.
5. Bloomfield CD, Garson OM, Volin L, Knuutila S, de la Chapelle A (1985): t(1;3)(p36;q21) in acute nanlymphocytic leukemia: A new cytogenetic-clinicopathologic association. Blood 66:1409-1413. 6. Grigg AP, Gascoyne RD, Phillips GL, Horsman DE (1993): Clinical, haematological and cytogenetic features in 24 patients with structural rearrangements of the Q arm of chromosome 3. Br J Haemato] 83:158-165. 7. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1991): Proposals for the recognition of minimally differentiated acute myeloid leukaemia. Br J Haematol 78:325-329. 8. Misawa S, Horiike S, Taniwaki J, Abe T, Takino T (1986): Prefixation treatment with ethidium bromide for high resoln-
tion banding analysis of chromosomes from cultured human bone marrow cells. Cancer Genet Cytogenet 22:319-329. 9. ISCN (1985): An International System for Human Cytogenetic Nomenclature. DG Harden and HP Klinger, eds. Karger, Basel. 10. Bellomo MJ, Parlier V, M~ihlematter D, Grob JP, Beris PH (1992): Three new cases of chromosome 3 rearrangement in bands q21 and q26 with abnormal thrombopoiesis bring further evidence to the existence of a 3q21q26 syndrome. Cancer Genet Cytogenet 59:138-160. 11. Suzukawa K, Satoh H, Taniwaki M, Yokota J, Morishita K (1995): The human thrombopoietin gene is located on chromosome 3q26.33-q27, but is not transcriptionally activated in leukemia cells with 3q21 and 3q26 abnormalities (3q21q26 syndrome). Leukemia 9:1328-1331. 12. Bouscary D, Fontenay-Roupie M, Chretien S, Hardy AC, Vigui6 F, Picard F, Melle J, Dreyfus F (1995): Thrombopoietin is not responsible for the thrombocytosis observed in
t(3;12)(q21;q24) in (AML-M0)
13.
14.
15.
16.
17.
18.
patients with acute myeloid leukemias and the 3q21q26 syndrome. Br J Haematol 91:425-427. Cigudosa JC, Calasanz MJ, Odero MD, Marin J. Bengoechea E, Gulldn A (1995): A recurrent translocation, t(3;11)(q21;q13), found in two distinct cases of acute myeloid leukemia. Cancer Genet Cytogenet 83:119-120. Yang F, Lure JB, McGill JR, Moore CM, Naylor SL, van Bragt PH, Baldwin WD, Bowman BH (1984): Human transferrin: cDNA characterization and chromosomal localization. Proc Natl Acad Sci USA 81:2752-2756. Lnsis AI, Rajavachisth TB, Klisak I, Heinzmann C, Mohandas T, Sparkes RS (1990): Mapping of the gene for CNBP, a finger protein, to human chromosome 3q13.3-q24. Genomics 8: 411--414. Nilsson MH, Spurr NK, Lundvall J, Rask L. Peterson PA (1988): Human cellular retinol-binding protein gene organization and chromosomal location. Eur J Biochem 173:35-44. Todorov I, Lavigne J, Sakr F, Kaneva R, Folsy S, Bibor-Hardy V (1991): Nuclear matrix protein mitotin mRNA is expressed at constant level during the cell cycle. Biochem Biophys Res Commun 177:395-400. Rousseau-Merck MF, Hillion J, Jonveaux P, Couillin P, Seit6 P, Thiesen HJ, Berger R (1993): Chromosomal localization of 9 KOX zinc finger genes: Physical linkage suggests clustering of KOX genes on chromosomes 12, 16, and 19. Hum Genet 92:583-587.
93
19. Huebner K, Druck T, Croce CM, Thiesen HJ (1991): Twentyseven nonover|apping zinc finger cDNAs from human T cells map to nine different chromosomes with apparent clustering. Am J Hum Genet 48:726-740. 20. Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J (1992): Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF). Genomics 13:293300. 21. Okumura K, Nogami M, Taguchi H, Dean FB, Chen M, Pan ZQ, Hurwitz J, Shiratori A, Murakami Y, Ozawa K, Eki T (1995): Assignment of the 36.5-kDa (RFC5), 37-kDa (RFC4), 38-kDa (RFC3), and 40-kDa (RFC2) subunit genes of human replication factor C to chromosome bands 12q24.2-q24.3, 3q27, 13q12.3-q13, and 7q11.23. Genomics 25:274-278. 22. Szpier J, Pedeutour F, Kesti T, Riviere M, Syvfioja JE, TurcCarel C, Szpirer C (1994): Localization of gene for DNA polymerase e (POLE) to human chromosome 12q24.3 and rat chromosome 12 by somatic cell hybrid panels and fluorescence in situ hybridization. Genomics 20:223-226. 23. Trent JM, Olson S, Lawn RM (1982): Chromosomal localization of human leukocyte, fibroblast, and immune interferon genes by means of in situ hybridization. Proc Natl Acad Sci USA 79:7809-7813.