case report inv (4)(p13q13) in patient with essential thrombocythemia: A case report Cigdem Aydin a, Ozan Salim b, Orhan Kemal Yucel b, Levent Undar b, Sibel Berker Karauzum
c,*
a Mehmet Akif Ersoy University, Bucak School of Health, Department of Nursing, Burdur, Turkey, b Akdeniz University, Faculty of Medicine, Department of Hematology, Antalya, Turkey, c Akdeniz University, Faculty of Medicine, Department of Medical Biology and Genetics, Antalya, Turkey
* Corresponding author. Tel.: +90 242 249 69 70. Æ [email protected] Æ Received for publication 16 October 2014 Æ Accepted for publication 11 April 2015 Hematol Oncol Stem Cell Ther 2015; 8(4): 181–184 ª 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). DOI: http://dx.doi.org/10.1016/j.hemonc.2015.04.003
The inv (4)(p13q13) cytogenetic abnormality is uncommon in hematologic malignancies. So far, it has not been previously reported in patients with essential thrombocythemia (ET). We report a first case of ET with inv (4)(p13q13) karyotype in a 69-year-old female patient who developed myelofibrosis at follow up. Conventional cytogenetic analysis from a bone marrow sample showed 46, XX, inv (4)(p13q13) [3]/46, XX [4] at diagnosis and subsequent analysis revealed the same abnormal karyotype during the myelofibrosis phase (46, XX, inv (4)(p13q13) [13]/46, XX [26]). The prognostic significance of this chromosomal abnormality is unknown. KEYWORDS: Essential thrombocythemia; Myeloproliferative disorder; inv (4)(p13q13)
E
ssential thrombocythemia (ET) is an acquired myeloproliferative disorder characterized by an increased number of platelets (>450 · 109/L) in the circulating blood. ET shares clinical, phenotypical and pathological similarities with other myeloproliferative neoplasms (MPNs), particularly polycythemia vera (PV) and primary myelofibrosis (PMF). ET is diagnosed by excluding the presence of other MPNs, and by excluding causes of reactive thrombocytosis. The incidence is approximately 1.5–2.5 per 100,000 population. The median age at diagnosis is 65–70 years, but the disease may occur at any age. The female to male ratio is approximately 2:1.1–4 The most common complications are vascular complications, including a tendency for thrombosis, microvascular disturbances, and hemorrhage.5 Survival of ET patients does not substantially differ from that of the general population. However, the main causes of morbidity are vascular complications. Transformation to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is an
Hematol Oncol Stem Cell Ther 8(4)
Fourth Quarter 2015
uncommon complication of ET, especially following therapy with alkylating agents or radioactive phosphorus.5,6 ET is a Philadelphia-negative classical myeloproliferative neoplasm, having much in common with other myeloproliferative neoplasms such as polycythemia vera and primary myelofibrosis.5 The Janus kinase 2 gene (JAK2) V617F mutation is detected in approximately 50% of patients diagnosed with ET.7,8 The incidence of clonal cytogenetic abnormalities in ET is approximately 5%, but no specific abnormality has been reported to date.9 We report a patient with essential thrombocythemia, presenting with the chromosomal abnormality: inv (4)(p13q13).
CASES REPORT In June 2012, a 69-year-old female patient was admitted to the internal medicine outpatient clinic with a complaint of excessive fatigue. Microcytic anemia and thrombocytosis (Hb: 6.6 g/dl, MCV: 72 fl,
181
case report WBC: 9.7 · 109/L, 1165 · 109/L) were detected in complete blood count. Microcytic anemia was consistent with iron deficiency anemia (IDA). Gastrointestinal blood loss was investigated as a possible cause of IDA. Colonoscopy and biopsy were consistent with the diagnosis of Crohn’s disease. IDA was successfully treated. During this period salazopyrine was started for Crohn’s disease. In retrospective analysis, thrombocytosis (approximately 1000 · 109/L) was determined to have been present for about 5 years. Despite successful treatment of IDA and Crohn’s disease, persistent thrombocytosis was observed, and a chronic myeloproliferative neoplasm was subsequently investigated. No other causes of reactive thrombocytosis were found. JAK-2 mutation analysis and t(9; 22) were negative in the peripheral blood. Hypercellular bone marrow and abundance of mature megakaryocytes and platelet clumps were observed. No significant increase in the erythroid and myeloid series and no other malignant infiltrations were observed. The patient’s karyotype was determined with conventional cytogenetic analysis in the bone marrow sample and was designated as 46, XX, inv (4)(p13q13) [3]/46, XX [4] according to the ISCN (International System for Human Cytogenetic Nomenclature) 2013 (Fig. 1). Our patient was diagnosed with essential thrombocythemia according to World Health Organization (WHO) 2008 criteria; and because of high-risk ET, acetylsalicylic acid and hydroxyurea therapy were initiated. The platelet count decreased with this treatment but due to the ensuing neutropenia it was discontinued and anagrelide (1 mg/day) was started. The patient was asymptomatic and her complete blood count was normal, except for mild anemia over a period of 1 year with this treatment. After this period, severe anemia occured and there were no causes to explain this anemia. She became transfusion-dependent and a leukoerythroblastic blood film was observed. At the same time, splenomegaly was observed with abdominal ultrasonography. A bone marrow biopsy was performed and this revealed grade III reticular myelofibrosis. The same cytogenetic abnormality was detected (46, XX, inv (4)(p13q13) [13]/46, XX [26]). She was diagnosed with post-essential thrombocythemia myelofibrosis (post-ET MF). She remains transfusion-dependent at follow up.
DISCUSSION ET is a chronic myeloproliferative neoplasm characterized by a persistent elevated platelet count in the peripheral blood and proliferation of enlarged
182
INV (4)(P13Q13) CYTOGENETIC ABNORMALITY
megakaryocytes in the bone marrow.10 Cytogenetic abnormalities in ET patients are very rare at diagnosis. Approximately 5% of ET patients show cytogenetic abnormalities which are non-specific. The most frequent cytogenetic abnormalities are trisomy 8, trisomy 9, and deletions of 13q and 20q.11,12 The role of these chromosomal abnormalities as prognostic indices in disease transformation is not sufficiently studied. In our case, persistent thrombocytosis was observed and a chronic myeloproliferative neoplasm was investigated. None of the cytogenetic abnormalities mentioned above in ET patients were detected in our patient. We observed a 46, XX, inv (4)(p13q13) [3]/46, XX [4] karyotype in our case with conventional cytogenetic analysis. This change is considered a clonal cytogenetic abnormality in ET because it is determined in 49% of metaphases. To our knowledge, an inv (4)(p13q13) cytogenetic abnormality has not been previously reported in patients with ET. Although these pericentric inversions of chromosome 4 have not been described in other myeloproliferative disorders, they have been observed in AML. The breakpoints determined in our case are different from inversions of chromosome 4 previously described in cases with AML.13–16 On the other hand, the same abnormality has been reported in only one case who has recurrent pregnancy loss.17 The breakpoint involved in the short arm of chromosome 4p13 in our case contains the RhoH/TTF (ARHH) gene. The RhoH gene encodes a member of the Ras superfamily of small GTPases and is restrictively expressed in hematopoietic cells and tissues.18 Its function in myeloid cells is unknown. Activation of this gene with mechanism of inversion may have an important role in the pathogenesis of ET or hematological malignancy. The inv (4)(p13q28) karyotype was previously reported in two patients diagnosed with AML 13. One of the breakpoints of the short arm of chromosome 4 (4p13) is the same as the breakpoint of our case. This finding may be associated with a transformation risk of ET patients to secondary myelofibrosis. This chromosomal abnormality was detected 2 years after the diagnosis, at which time post-ET MF had developed. As far as we know, the other breakpoint of inversion (4q13) does not contain any gene that has been associated with ET or hematological malignancies as yet. This is the first reported case of inv (4)(p13q13) karyotype in ET. The prognostic significance and transformation to myelofibrosis or AML, associated
Hematol Oncol Stem Cell Ther 8(4)
Fourth Quarter 2015
case report
INV (4)(P13Q13) CYTOGENETIC ABNORMALITY
Fig. 1. Representative karyogram of bone marrow cells showing 46, XX, inv (4)(p13q13) karyotype.
with this abnormality is not known. There are some possible molecular mechanisms that could be associated with AML transformation. The RhoH gene, which is associated with the breakpoint of chromosome 4p, might be responsible for this relation. However, these possible mechanisms and our findings need to be confirmed and studied in further cases with ET. For all the reasons mentioned above, our patient should be followed-up closely with cytogenetic analysis and molecular cytogenetic analysis and molecular
cytogenetic techniques for a possible higher risk of AML transformation.
CONFLICT OF INTEREST The authors declare no conflict of interest regarding the publication of this paper. Acknowledgment This work is supported by the Akdeniz University Scientific Projects Management Unit.
REFERENCES 1. Brire JB. Essential thrombocythemia. Orphanet J Rare Dis 2007;2:3. 2. Beer PA, Erber WN, Campbell PJ, Green AR. How I treat essential thrombocythemia. Blood 2011;117(5):1472–82. 3. Beer PA, Green AR. Pathogenesis and management of essential thrombocythemia. Hematol Am Soc Hematol Educ Program 2009:621–8. 4. Johansson P. Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 2006;32(3):171–3. 5. Bernasconi P, Boni M, Cavigliano PM, Calatroni S, Brusamolino E, Passamonti F, et al. Acute myeloid leukemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea. Leukemia 2002;16(10):2078–83.
Hematol Oncol Stem Cell Ther 8(4)
6. Sterkers Y, Preudhomme C, La JL, Demory JL, Caulier MT, Wattel E, et al. Acute myeloid leukemia and myelodysplastic syndrome following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood 1998;91(2):616–22. 7. Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V > F mutation in patients with polycythemia vera or essential thrombocythemia. Blood 2007;110(3):840–6. 8. Antonioli E, Guglielmelli P, Pancrazzi A, Bogani C, Verrucci M, Ponziani V, et al. Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. Leukemia 2005;19(10):1847–9. 9. Mittelman F. The third international workshop on chromosomes in leukemia. Lund, Sweden, July 21– 25, 1980. Introduction. Cancer Genet Cytogenet 1981;4(2):96–8.
Fourth Quarter 2015
10. Michiels JJ, Thiele J. Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). Int J Hematol 2002;76(2):133–45. 11. Zamora L, Espinet B, Florensa L, Besses C, Salido M, Sol F. Incidence of trisomy 8 and 9, deletion of D13S319 and D20S108 loci and BCR/ABL translocation in non-treated essential thrombocythemia patients: an analysis of bone marrow cells using interphase fluorescence in situ hybridization. Haematologica 2003;88(1):110–1. 12. Panani AD. Cytogenetic findings in untreated patients with essential thrombocythemia. In Vivo 2006;20(3):381–4. 13. Iurlo A, Mecucci C, Van Orshoven A, Michaux JL, Van den Berghe H. Inversion (4)(p13q28) in two cases of acute nonlymphocytic leukemia. Cancer Genet Cytogenet 1988;36(2):143–7.
183
case report 14. Bloom RE, Brennan JK, Sullivan JL, Chiganti RS, Dinsmore R, O'Reilly R. Lymphoma of host origin in a marrow transplant recipient in remission of acute myeloid leukemia and receiving cyclosporin A. Am J Hematol 1985;18(1):73–83. 15. Sreekantaiah C, Han T, Baer MR, Sandberg AA. Acute nonlymphocytic leukemia in a patient with a constitutional inv(4). Cancer Genet Cytogenet 1989;39(1):119–23.
184
INV (4)(P13Q13) CYTOGENETIC ABNORMALITY 16. Benasayag S, Arias E, Baialardo E, Reyes M, Sapia S, Bistmans A, et al. Inv(4)(p14q27) in a case with de novo acute nonlymphocytic leukemia. Acta Haematol 2002;108(1):39–42. 17. Verma RS, Kleyman SM. Incidence of breakpoints in pericentric inversions of chromosome 4. Ann Genet 1996;39(4):243–5. 18. Dallery-Prudhomme E, Roumier C, Denis C, Preudhomme C, Kerckaert JP, Galiegue-Zouitina S.
Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization. Genomics 1997;43(1):89–94.
Hematol Oncol Stem Cell Ther 8(4)
Fourth Quarter 2015
c,*
a Mehmet Akif Ersoy University, Bucak School of Health, Department of Nursing, Burdur, Turkey, b Akdeniz University, Faculty of Medicine, Department of Hematology, Antalya, Turkey, c Akdeniz University, Faculty of Medicine, Department of Medical Biology and Genetics, Antalya, Turkey
* Corresponding author. Tel.: +90 242 249 69 70. Æ [email protected] Æ Received for publication 16 October 2014 Æ Accepted for publication 11 April 2015 Hematol Oncol Stem Cell Ther 2015; 8(4): 181–184 ª 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). DOI: http://dx.doi.org/10.1016/j.hemonc.2015.04.003
The inv (4)(p13q13) cytogenetic abnormality is uncommon in hematologic malignancies. So far, it has not been previously reported in patients with essential thrombocythemia (ET). We report a first case of ET with inv (4)(p13q13) karyotype in a 69-year-old female patient who developed myelofibrosis at follow up. Conventional cytogenetic analysis from a bone marrow sample showed 46, XX, inv (4)(p13q13) [3]/46, XX [4] at diagnosis and subsequent analysis revealed the same abnormal karyotype during the myelofibrosis phase (46, XX, inv (4)(p13q13) [13]/46, XX [26]). The prognostic significance of this chromosomal abnormality is unknown. KEYWORDS: Essential thrombocythemia; Myeloproliferative disorder; inv (4)(p13q13)
E
ssential thrombocythemia (ET) is an acquired myeloproliferative disorder characterized by an increased number of platelets (>450 · 109/L) in the circulating blood. ET shares clinical, phenotypical and pathological similarities with other myeloproliferative neoplasms (MPNs), particularly polycythemia vera (PV) and primary myelofibrosis (PMF). ET is diagnosed by excluding the presence of other MPNs, and by excluding causes of reactive thrombocytosis. The incidence is approximately 1.5–2.5 per 100,000 population. The median age at diagnosis is 65–70 years, but the disease may occur at any age. The female to male ratio is approximately 2:1.1–4 The most common complications are vascular complications, including a tendency for thrombosis, microvascular disturbances, and hemorrhage.5 Survival of ET patients does not substantially differ from that of the general population. However, the main causes of morbidity are vascular complications. Transformation to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is an
Hematol Oncol Stem Cell Ther 8(4)
Fourth Quarter 2015
uncommon complication of ET, especially following therapy with alkylating agents or radioactive phosphorus.5,6 ET is a Philadelphia-negative classical myeloproliferative neoplasm, having much in common with other myeloproliferative neoplasms such as polycythemia vera and primary myelofibrosis.5 The Janus kinase 2 gene (JAK2) V617F mutation is detected in approximately 50% of patients diagnosed with ET.7,8 The incidence of clonal cytogenetic abnormalities in ET is approximately 5%, but no specific abnormality has been reported to date.9 We report a patient with essential thrombocythemia, presenting with the chromosomal abnormality: inv (4)(p13q13).
CASES REPORT In June 2012, a 69-year-old female patient was admitted to the internal medicine outpatient clinic with a complaint of excessive fatigue. Microcytic anemia and thrombocytosis (Hb: 6.6 g/dl, MCV: 72 fl,
181
case report WBC: 9.7 · 109/L, 1165 · 109/L) were detected in complete blood count. Microcytic anemia was consistent with iron deficiency anemia (IDA). Gastrointestinal blood loss was investigated as a possible cause of IDA. Colonoscopy and biopsy were consistent with the diagnosis of Crohn’s disease. IDA was successfully treated. During this period salazopyrine was started for Crohn’s disease. In retrospective analysis, thrombocytosis (approximately 1000 · 109/L) was determined to have been present for about 5 years. Despite successful treatment of IDA and Crohn’s disease, persistent thrombocytosis was observed, and a chronic myeloproliferative neoplasm was subsequently investigated. No other causes of reactive thrombocytosis were found. JAK-2 mutation analysis and t(9; 22) were negative in the peripheral blood. Hypercellular bone marrow and abundance of mature megakaryocytes and platelet clumps were observed. No significant increase in the erythroid and myeloid series and no other malignant infiltrations were observed. The patient’s karyotype was determined with conventional cytogenetic analysis in the bone marrow sample and was designated as 46, XX, inv (4)(p13q13) [3]/46, XX [4] according to the ISCN (International System for Human Cytogenetic Nomenclature) 2013 (Fig. 1). Our patient was diagnosed with essential thrombocythemia according to World Health Organization (WHO) 2008 criteria; and because of high-risk ET, acetylsalicylic acid and hydroxyurea therapy were initiated. The platelet count decreased with this treatment but due to the ensuing neutropenia it was discontinued and anagrelide (1 mg/day) was started. The patient was asymptomatic and her complete blood count was normal, except for mild anemia over a period of 1 year with this treatment. After this period, severe anemia occured and there were no causes to explain this anemia. She became transfusion-dependent and a leukoerythroblastic blood film was observed. At the same time, splenomegaly was observed with abdominal ultrasonography. A bone marrow biopsy was performed and this revealed grade III reticular myelofibrosis. The same cytogenetic abnormality was detected (46, XX, inv (4)(p13q13) [13]/46, XX [26]). She was diagnosed with post-essential thrombocythemia myelofibrosis (post-ET MF). She remains transfusion-dependent at follow up.
DISCUSSION ET is a chronic myeloproliferative neoplasm characterized by a persistent elevated platelet count in the peripheral blood and proliferation of enlarged
182
INV (4)(P13Q13) CYTOGENETIC ABNORMALITY
megakaryocytes in the bone marrow.10 Cytogenetic abnormalities in ET patients are very rare at diagnosis. Approximately 5% of ET patients show cytogenetic abnormalities which are non-specific. The most frequent cytogenetic abnormalities are trisomy 8, trisomy 9, and deletions of 13q and 20q.11,12 The role of these chromosomal abnormalities as prognostic indices in disease transformation is not sufficiently studied. In our case, persistent thrombocytosis was observed and a chronic myeloproliferative neoplasm was investigated. None of the cytogenetic abnormalities mentioned above in ET patients were detected in our patient. We observed a 46, XX, inv (4)(p13q13) [3]/46, XX [4] karyotype in our case with conventional cytogenetic analysis. This change is considered a clonal cytogenetic abnormality in ET because it is determined in 49% of metaphases. To our knowledge, an inv (4)(p13q13) cytogenetic abnormality has not been previously reported in patients with ET. Although these pericentric inversions of chromosome 4 have not been described in other myeloproliferative disorders, they have been observed in AML. The breakpoints determined in our case are different from inversions of chromosome 4 previously described in cases with AML.13–16 On the other hand, the same abnormality has been reported in only one case who has recurrent pregnancy loss.17 The breakpoint involved in the short arm of chromosome 4p13 in our case contains the RhoH/TTF (ARHH) gene. The RhoH gene encodes a member of the Ras superfamily of small GTPases and is restrictively expressed in hematopoietic cells and tissues.18 Its function in myeloid cells is unknown. Activation of this gene with mechanism of inversion may have an important role in the pathogenesis of ET or hematological malignancy. The inv (4)(p13q28) karyotype was previously reported in two patients diagnosed with AML 13. One of the breakpoints of the short arm of chromosome 4 (4p13) is the same as the breakpoint of our case. This finding may be associated with a transformation risk of ET patients to secondary myelofibrosis. This chromosomal abnormality was detected 2 years after the diagnosis, at which time post-ET MF had developed. As far as we know, the other breakpoint of inversion (4q13) does not contain any gene that has been associated with ET or hematological malignancies as yet. This is the first reported case of inv (4)(p13q13) karyotype in ET. The prognostic significance and transformation to myelofibrosis or AML, associated
Hematol Oncol Stem Cell Ther 8(4)
Fourth Quarter 2015
case report
INV (4)(P13Q13) CYTOGENETIC ABNORMALITY
Fig. 1. Representative karyogram of bone marrow cells showing 46, XX, inv (4)(p13q13) karyotype.
with this abnormality is not known. There are some possible molecular mechanisms that could be associated with AML transformation. The RhoH gene, which is associated with the breakpoint of chromosome 4p, might be responsible for this relation. However, these possible mechanisms and our findings need to be confirmed and studied in further cases with ET. For all the reasons mentioned above, our patient should be followed-up closely with cytogenetic analysis and molecular cytogenetic analysis and molecular
cytogenetic techniques for a possible higher risk of AML transformation.
CONFLICT OF INTEREST The authors declare no conflict of interest regarding the publication of this paper. Acknowledgment This work is supported by the Akdeniz University Scientific Projects Management Unit.
REFERENCES 1. Brire JB. Essential thrombocythemia. Orphanet J Rare Dis 2007;2:3. 2. Beer PA, Erber WN, Campbell PJ, Green AR. How I treat essential thrombocythemia. Blood 2011;117(5):1472–82. 3. Beer PA, Green AR. Pathogenesis and management of essential thrombocythemia. Hematol Am Soc Hematol Educ Program 2009:621–8. 4. Johansson P. Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 2006;32(3):171–3. 5. Bernasconi P, Boni M, Cavigliano PM, Calatroni S, Brusamolino E, Passamonti F, et al. Acute myeloid leukemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea. Leukemia 2002;16(10):2078–83.
Hematol Oncol Stem Cell Ther 8(4)
6. Sterkers Y, Preudhomme C, La JL, Demory JL, Caulier MT, Wattel E, et al. Acute myeloid leukemia and myelodysplastic syndrome following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood 1998;91(2):616–22. 7. Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V > F mutation in patients with polycythemia vera or essential thrombocythemia. Blood 2007;110(3):840–6. 8. Antonioli E, Guglielmelli P, Pancrazzi A, Bogani C, Verrucci M, Ponziani V, et al. Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. Leukemia 2005;19(10):1847–9. 9. Mittelman F. The third international workshop on chromosomes in leukemia. Lund, Sweden, July 21– 25, 1980. Introduction. Cancer Genet Cytogenet 1981;4(2):96–8.
Fourth Quarter 2015
10. Michiels JJ, Thiele J. Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). Int J Hematol 2002;76(2):133–45. 11. Zamora L, Espinet B, Florensa L, Besses C, Salido M, Sol F. Incidence of trisomy 8 and 9, deletion of D13S319 and D20S108 loci and BCR/ABL translocation in non-treated essential thrombocythemia patients: an analysis of bone marrow cells using interphase fluorescence in situ hybridization. Haematologica 2003;88(1):110–1. 12. Panani AD. Cytogenetic findings in untreated patients with essential thrombocythemia. In Vivo 2006;20(3):381–4. 13. Iurlo A, Mecucci C, Van Orshoven A, Michaux JL, Van den Berghe H. Inversion (4)(p13q28) in two cases of acute nonlymphocytic leukemia. Cancer Genet Cytogenet 1988;36(2):143–7.
183
case report 14. Bloom RE, Brennan JK, Sullivan JL, Chiganti RS, Dinsmore R, O'Reilly R. Lymphoma of host origin in a marrow transplant recipient in remission of acute myeloid leukemia and receiving cyclosporin A. Am J Hematol 1985;18(1):73–83. 15. Sreekantaiah C, Han T, Baer MR, Sandberg AA. Acute nonlymphocytic leukemia in a patient with a constitutional inv(4). Cancer Genet Cytogenet 1989;39(1):119–23.
184
INV (4)(P13Q13) CYTOGENETIC ABNORMALITY 16. Benasayag S, Arias E, Baialardo E, Reyes M, Sapia S, Bistmans A, et al. Inv(4)(p14q27) in a case with de novo acute nonlymphocytic leukemia. Acta Haematol 2002;108(1):39–42. 17. Verma RS, Kleyman SM. Incidence of breakpoints in pericentric inversions of chromosome 4. Ann Genet 1996;39(4):243–5. 18. Dallery-Prudhomme E, Roumier C, Denis C, Preudhomme C, Kerckaert JP, Galiegue-Zouitina S.
Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization. Genomics 1997;43(1):89–94.
Hematol Oncol Stem Cell Ther 8(4)
Fourth Quarter 2015
