- Email: [email protected]
Two additional ANLL cases with chromosome 3 rearrangements involving bands q21 and q26
ELSEVIER
LETTERS TO THE EDITOR Two Additional ANLL Cases With Chromosome 3 Rearrangements Involving Bands q21 and q26
Acquired structural alterations of the long arm of chromosome 3 involving bands q21 and q26 have been reported in cases of acute nonlymphocytic leukemia (ANLL), myelodysplastic syndrome, blast phase of chronic myeloid leukemia, polycythemia vera, and myelofibrosis with myeloid metaplasia [1]. In most patients, 3q rearrangements are associated with normal or elevated platelet count, hyperplasia and dysplasia of bone marrow megakaryocytes, dysplasia of myeloid and erythroid lineages, and poor prognosis [1, 2]. Here we describe two additional patients with structural abnormalities of long arm of chromosome 3 involving bands q21 and q26. The first patient, a 56-year-old man, was admitted to the hospital in July 1993 with asthenia. Physical examination was unremarkable. The hemogram revealed: hemoglobin 8.6 gr/dL, hematocrit 27.8%, MCV 92.4 fL, reticulocytes 0.08% white blood cell (WBC) count 7.6 × 109/L (10% neutrophils, 44% lymphocytes, 4% monocytes, 2% myelocytes, 6% metamyelocytes, and 34% blasts), and platelets 1650 × 109/L. Bone marrow (BM) aspirate revealed trilineage dysplasia. Hyperplasia and dysplasia of megakaryocytes was marked, with micromegakaryocytes and megakaryocytes with separate nuclei. Cytochemistry studies were positive for ANAE (53%), Black Sudan B (12%), and peroxidase (9%). Inmunophenotype studies were positive for CD13, CD14, CD33, and CD68. Chromosome analysis was performed on BM cells after a 24-hour culture. The cytogenetic study revealed 45,X,-Y,t(3;3)(q21;q26). The diagnosis of ANLL type M5a was made. Treatment with polychemotherapy was started. The patient showed a poor response to therapy and died of pulmonary infection 1 year after the diagnosis. The second patient, a 35-year-old woman, was admitted to the hospital in May 1994 with asthenia and headache. Physical examination was unremarkable. Blood count was as follows: Hemoglobin level 7.6 gr/dL, hematocrit 23.3%, MCV 91 fL, WBC count 7.6 × 109/L (54% neutrophils, 24% lymphocytes, 1% monocytes, and 21% blasts), and platelets 367 × 109/L. BM aspirate showed trilineage dysplasia. Hyperplasia and dysplasia of megakaryocytes with separate nuclei were observed. Cytochemistry was positive for ANAE (36%). Immunophenotype studies were positive for CD34, HLA-DR, CKIT, CD13, and CD33. Chromosome analysis was performed on BM cells after a 24-hour culture. The cytogenetic study showed 46,XX, Cancer Genet Cytogenet 88:90-91 (1996) © Elsevier Science Inc., 1996 655 Avenue of the Americas, New York, NY 10010
inv(3)(q21q26). The diagnosis of ANLL FAB type M0 was made. Treatment with polychemotherapy was started. An allogenic BM transplantation was attempted despite the presence of residual disease. The patient had a poor response to therapy and died 12 months after the initial diagnosis. Comparison of a number of literature cases of ANLL with abnormalities of chromosome 3 has confirmed the existence of a 3q21q26 syndrome. This syndrome is characterized by normal or elevated platelet count, multilineage involvement, short duration of myelodysplastic phases, and poor prognosis [1]. Fonastch et al. [3] have speculated that, whereas the translocation t(3;3) seems to be sufficient for the outbreak of an overt leukemia, the inversion of chromosome 3 may trigger additional chromosome changes leading to disease aggravation. The case described here with inv(3)(q21q26), presenting the characteristic features of a 3q21q26 syndrome, suggests that this hypothesis does not hold true for all the patients with this rearrangement. The ectopic expression of the EVIl gene in hematopoietic cells has been associated with transformation [2]. The basis of transformation is not defined, although it may be related to the DNA-binding properties of the EVIl protein. On the other hand, abnormal expression of the EVIl gene has been implicated in cases of AML with inv(3)(q21q26) [2, 4]. Recently, it has been suggested that the transcriptional activation of the EVIl gene in the translocations and inversions involving bands 3q21 and 3q26 is caused by the introduction of enhancer elements of the ribophorin I gene [4]. Further studies on the breakpoint regions and the suggested mechanisms related to the development of the 3q21q26 syndrome may help to elucidate its pathogenesis. S. BORREGO G. ANTIIQOLO J. PRIETO
U n i d a d de Gen6tica M6dica
Servicio de Hematologfa Hospital Universitario Virgen del Rocfo, Seville, Spain
REFERENCES
1. Jotterand Bellomo M, Parlier V, Miihlematter D, Grob JP, Beris Ph (1992): Three new cases of chromosome 3 rearrangement
0165-4608/96/$15.00 SSDI 0165-4608(95)00310-X
Age a n d Cytogenetics i n MDS
in bands q21 and q26 with abnormal thrombopoiesis bring further evidence to the existence of a 3q21q26 syndrome. Cancer Genet Cytogenet 59:138-160. 2. Levy ER, Parganas E, Morishita K, Fichelson S, James L, Oscier D, Gisselbrecht S, Ihle JN, Buckle VJ (1994): DNA rearrangement proximal to the EVIl locus associated with the 3q21q26 syndrome. Blood 83:1348-1354. 3. Fonatsch C, Gudat H, Lengfelder E, Wandt H, Silling-Engel-
91
hardt G, Ludwig WD, Thiel E, Freund M, Bodenstein H, Rieder H, Haase D, Hild F (1994): Correlation of cytogenetic findings with clinical features in 18 patients with inv(3)(q21q26) or t(3;3)(q21;q26). Leukemia 8:1318-1326. 4. Suzukawa K, Parganas E, Gajjar A, Abe T, Takahashi S, Tani K, Asano S, Asou H, Kamada N, Yokota J, Morishita K, Ihle J (1994): Identification of a breakpoint cluster region 3 of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVIl gene in acute myelogenous leukemias with inv(3)(q21q26). Blood 84:2681-2688.
LETTERS TO THE EDITOR Two Additional ANLL Cases With Chromosome 3 Rearrangements Involving Bands q21 and q26
Acquired structural alterations of the long arm of chromosome 3 involving bands q21 and q26 have been reported in cases of acute nonlymphocytic leukemia (ANLL), myelodysplastic syndrome, blast phase of chronic myeloid leukemia, polycythemia vera, and myelofibrosis with myeloid metaplasia [1]. In most patients, 3q rearrangements are associated with normal or elevated platelet count, hyperplasia and dysplasia of bone marrow megakaryocytes, dysplasia of myeloid and erythroid lineages, and poor prognosis [1, 2]. Here we describe two additional patients with structural abnormalities of long arm of chromosome 3 involving bands q21 and q26. The first patient, a 56-year-old man, was admitted to the hospital in July 1993 with asthenia. Physical examination was unremarkable. The hemogram revealed: hemoglobin 8.6 gr/dL, hematocrit 27.8%, MCV 92.4 fL, reticulocytes 0.08% white blood cell (WBC) count 7.6 × 109/L (10% neutrophils, 44% lymphocytes, 4% monocytes, 2% myelocytes, 6% metamyelocytes, and 34% blasts), and platelets 1650 × 109/L. Bone marrow (BM) aspirate revealed trilineage dysplasia. Hyperplasia and dysplasia of megakaryocytes was marked, with micromegakaryocytes and megakaryocytes with separate nuclei. Cytochemistry studies were positive for ANAE (53%), Black Sudan B (12%), and peroxidase (9%). Inmunophenotype studies were positive for CD13, CD14, CD33, and CD68. Chromosome analysis was performed on BM cells after a 24-hour culture. The cytogenetic study revealed 45,X,-Y,t(3;3)(q21;q26). The diagnosis of ANLL type M5a was made. Treatment with polychemotherapy was started. The patient showed a poor response to therapy and died of pulmonary infection 1 year after the diagnosis. The second patient, a 35-year-old woman, was admitted to the hospital in May 1994 with asthenia and headache. Physical examination was unremarkable. Blood count was as follows: Hemoglobin level 7.6 gr/dL, hematocrit 23.3%, MCV 91 fL, WBC count 7.6 × 109/L (54% neutrophils, 24% lymphocytes, 1% monocytes, and 21% blasts), and platelets 367 × 109/L. BM aspirate showed trilineage dysplasia. Hyperplasia and dysplasia of megakaryocytes with separate nuclei were observed. Cytochemistry was positive for ANAE (36%). Immunophenotype studies were positive for CD34, HLA-DR, CKIT, CD13, and CD33. Chromosome analysis was performed on BM cells after a 24-hour culture. The cytogenetic study showed 46,XX, Cancer Genet Cytogenet 88:90-91 (1996) © Elsevier Science Inc., 1996 655 Avenue of the Americas, New York, NY 10010
inv(3)(q21q26). The diagnosis of ANLL FAB type M0 was made. Treatment with polychemotherapy was started. An allogenic BM transplantation was attempted despite the presence of residual disease. The patient had a poor response to therapy and died 12 months after the initial diagnosis. Comparison of a number of literature cases of ANLL with abnormalities of chromosome 3 has confirmed the existence of a 3q21q26 syndrome. This syndrome is characterized by normal or elevated platelet count, multilineage involvement, short duration of myelodysplastic phases, and poor prognosis [1]. Fonastch et al. [3] have speculated that, whereas the translocation t(3;3) seems to be sufficient for the outbreak of an overt leukemia, the inversion of chromosome 3 may trigger additional chromosome changes leading to disease aggravation. The case described here with inv(3)(q21q26), presenting the characteristic features of a 3q21q26 syndrome, suggests that this hypothesis does not hold true for all the patients with this rearrangement. The ectopic expression of the EVIl gene in hematopoietic cells has been associated with transformation [2]. The basis of transformation is not defined, although it may be related to the DNA-binding properties of the EVIl protein. On the other hand, abnormal expression of the EVIl gene has been implicated in cases of AML with inv(3)(q21q26) [2, 4]. Recently, it has been suggested that the transcriptional activation of the EVIl gene in the translocations and inversions involving bands 3q21 and 3q26 is caused by the introduction of enhancer elements of the ribophorin I gene [4]. Further studies on the breakpoint regions and the suggested mechanisms related to the development of the 3q21q26 syndrome may help to elucidate its pathogenesis. S. BORREGO G. ANTIIQOLO J. PRIETO
U n i d a d de Gen6tica M6dica
Servicio de Hematologfa Hospital Universitario Virgen del Rocfo, Seville, Spain
REFERENCES
1. Jotterand Bellomo M, Parlier V, Miihlematter D, Grob JP, Beris Ph (1992): Three new cases of chromosome 3 rearrangement
0165-4608/96/$15.00 SSDI 0165-4608(95)00310-X
Age a n d Cytogenetics i n MDS
in bands q21 and q26 with abnormal thrombopoiesis bring further evidence to the existence of a 3q21q26 syndrome. Cancer Genet Cytogenet 59:138-160. 2. Levy ER, Parganas E, Morishita K, Fichelson S, James L, Oscier D, Gisselbrecht S, Ihle JN, Buckle VJ (1994): DNA rearrangement proximal to the EVIl locus associated with the 3q21q26 syndrome. Blood 83:1348-1354. 3. Fonatsch C, Gudat H, Lengfelder E, Wandt H, Silling-Engel-
91
hardt G, Ludwig WD, Thiel E, Freund M, Bodenstein H, Rieder H, Haase D, Hild F (1994): Correlation of cytogenetic findings with clinical features in 18 patients with inv(3)(q21q26) or t(3;3)(q21;q26). Leukemia 8:1318-1326. 4. Suzukawa K, Parganas E, Gajjar A, Abe T, Takahashi S, Tani K, Asano S, Asou H, Kamada N, Yokota J, Morishita K, Ihle J (1994): Identification of a breakpoint cluster region 3 of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVIl gene in acute myelogenous leukemias with inv(3)(q21q26). Blood 84:2681-2688.