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Chung, Seo, Kim, Jang, Park, Chi, Lee, Lee, and Lee: Hematologic and Clinical Features of 3q21q26 Syndrome: Extremely Poor Prognosis and Association with Central Diabetes Insipidus
Original Article

Korean J Leg Med 2007;27(2):133-138.

Published online: 10 February 2007

DOI: https://doi.org/10.3343/kjlm.2007.27.2.133

Hematologic and Clinical Features of 3q21q26 Syndrome: Extremely Poor Prognosis and Association with Central Diabetes Insipidus

Hee-Jung Chung, M.D.1, Eul-Ju Seo, M.D.1, Kyung-Hee Kim, M.D.1, Seongsoo Jang, M.D.1, Chan-Jeoung Park, M.D.1, Hyun-Sook Chi, M.D.1, Jung-Hee Lee, M.D.2, Je-Hwan Lee, M.D.2, Kyu-Hyung Lee, M.D.2

1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea

2Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea

Received 26 October 2006       Revised 20 December 2006       Accepted 2 January 2007

Copyright © 2007 The Korean Society for Legal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

3q21q26 syndrome includes chromosomal abnormalities of inv(3)(q21q26), t(3;3) (q21;q26), and ins(3;3)(q26;q21q26). It causes hematological diseases by the leukemogenic mechanism that the enhancer of ribophorin I gene in 3q21 induces the transcription of ecotropic viral integration site-1 gene in 3q26. Recently, it has been proposed that the 3q21q26 syndrome may be preceded by diabetes insipidus (DI), particularly when combined with monosomy 7, and is a unique disease entity.

Methods

From May 2001 to June 2006, a total of 5 patients with hematologic malignancy were found to have 3q21q26 syndrome and monosomy 7. Laboratory findings, clinical data, and association with DI were investigated.

Results

The rearrangement type of 3q21q26 was inv(3)(q21q26) in four patients and t(3;3)(q21;q26) in one. These patients' French American British types were AML M1, M2, M4 and M7, showing evident dysmegakaryopoiesis. Aberrant antigenic expressions of CD7 and CD56 were observed. The platelet count was relatively high as AML. All the five patients were refractory or in early relapse. Patient 5 was diagnosed with AML M7 20 days after being diagnosed with DI. While DI was well controlled with oral desmopressin, leukemia was refractory to chemotherapy.

Conclusions

This study supports the recent opinion that 3q21q26 syndrome with monosomy 7 combined with DI is a disease of unique characteristics. In the relation between DI and monosomy 7 or 3q21q26 syndrome, there has been no explanation about how acquired abnormality of hematopoietic cells affects production of DDAVP by neurohormonal cells in hypothalamus. The mechanism needs further study, and this research should contribute to the understanding of genetic roles in leukemia appearing in different forms.

Keywords: 3q21q26, Chromosome 3q, Monosomy 7, Diabetes insipidus

References

1. Testoni N, Borsaru G, Martinelli G, Carboni C, Ruggeri D, Ottaviani E, et al. 3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features. Haematologica. 1999; 84:690–4.
2. Ogawa S, Kurokawa M, Tanaka T, Mitani K, Inazawa J, Hangaishi A, et al. Structurally altered Evi-1 protein generated in the 3q21q26 syndrome. Oncogene. 1996; 13:183–91.
3. Breccia M, Petti MC, Ottaviani E, Mancini M, D'Elia GM, Mecarocci S, et al. Diabetes insipidus as first manifestation of acute myeloid leukaemia with EVI-1-positive, 3q21q26 syndrome and T cell-line antigen expression: what is the EVI-1 gene role? Br J Haematol. 2002; 118:438–41.
crossref
4. Keung YK, Buss D, Powell BL, Pettenati M. Central diabetes insipidus and inv(3)(q21q26) and monosomy 7 in acute myeloid leukemia. Cancer Genet Cytogenet. 2002; 136:78–81.
crossref
5. Lavabre-Bertrand T, Bourquard P, Chiesa J, Bertheas MF, Lefort G, Taib J, et al. Diabetes insipidus revealing acute myelogenous leukaemia with a high platelet count, monosomy 7 and abnormalities of chromosome 3: a new entity? Eur J Haematol. 2001; 66:66–9.
crossref
6. Fujisawa S, Tanabe J, Harano H, Kanamori H, Motomura S, Mohri H, et al. Acute minimally differentiated myeloid leukemia (M0) with inv(3)(q21q26). Leuk Lymphoma. 1999; 35:627–30.
crossref
7. Muller CI, Engelhardt M, Laubenberger J, Kunzmann R, Engelhardt R, Lubbert M. Myelodysplastic syndrome in transformation to acute myeloid leukemia presenting with diabetes insipidus: due to pituitary infiltration association with abnormalities of chromosomes 3 and 7. Eur J Haematol. 2002; 69:115–9.
8. Lahortiga I, Vazquez I, Agirre X, Larrayoz MJ, Vizmanos JL, Gozzetti A, et al. Molecular heterogeneity in AML/MDS patients with 3q21q26 rearrangements. Genes Chromosomes Cancer. 2004; 40:179–89.
crossref
9. Schmidt HH, Pirc-Danoewinata H, Linkesch W, Strunk D, Wieser R. inv(3)(q21q26) in AML/MDS: monitoring of the malignant clone with interphase FISH. Haematologica. 2003; 88:ECR38.
10. Secker-Walker LM, Mehta A, Bain B. Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study. Br J Haematol. 1995; 91:490–501.
crossref
11. Shi G, Weh HJ, Duhrsen U, Zeller W, Hossfeld DK. Chromosomal abnormality inv(3)(q21q26) associated with multilineage hematopoietic progenitor cells in hematopoietic malignancies. Cancer Genet Cytogenet. 1997; 96:58–63.
crossref
12. Shaffer LG, Tommerup N, editors. An International System for Human Cytogenetics Nomenclature (ISCN). Basel: Karger;2005.
13. Lee CL. Double inversion (3)(q21q26) and monosomy 7 in a case of acute myeloid leukemia. Cancer Genet Cytogenet. 1999; 111:99–101.
14. Schnittger S, Schoch C, Streubel B, Hinrichs HF, Otremba B, Parwaresch R, et al. A case of atypical myelodysplastic syndrome with micromegakaryocytes, normal platelet count, and t(3;12)(q21;p13) with inv(3)(q21q26). Genes Chromosomes Cancer. 1997; 20:292–8.
crossref
15. Bouscary D, Fontenay-Roupie M, Chretien S, Hardy AC, Viguie F, Picard F, et al. Thrombopoietin is not responsible for the thrombocytosis observed in patients with acute myeloid leukemias and the 3q21q26 syndrome. Br J Haematol. 1995; 91:425–7.
crossref
16. Schnittger S, de Sauvage FJ, Le Paslier D, Fonatsch C. Refined chromosomal localization of the human thrombopoietin gene to 3q27-q28 and exclusion as the responsible gene for thrombocytosis in patients with rearrangements of 3q21 and 3q26. Leukemia. 1996; 10:1891–6.
17. Lee YH, Lee KA, Kim SH. 3q chromosomal abnormalities associated with dysmegakaryopoiesis in acute leukemias. Korean J Clin Pathol. 2001; 21:18–23.
18. Reiter E, Greinix H, Rabitsch W, Keil F, Schwarzinger I, Jaeger U, et al. Low curative potential of bone marrow transplantation for highly aggressive acute myelogenous leukemia with inversioin inv (3)(q21-q26) or homologous translocation t(3;3) (q21;q26). Ann Hematol. 2000; 79:374–7.
19. Jolkowska J, Witt M. The EVI-1 gene–its role in pathogenesis of human leukemias. Leuk Res. 2000; 24:553–8.
20. Buonamici S, Chakraborty S, Senyuk V, Nucifora G. The role of EVI1 in normal and leukemic cells. Blood Cells Mol Dis. 2003; 31:206–12.
crossref
21. Nucifora G, Laricchia-Robbio L, Senyuk V. EVI1 and hematopoietic disorders: history and perspectives. Gene. 2006; 368:1–11.
crossref
22. Nieboer P, Vellenga E, Adriaanse R, van de Loosdrecht AA. Central diabetes insipidus preceding acute myeloid leukemia with t(3;12) (q26;p12). Neth J Med. 2000; 56:45–7.
23. Kollen WJ, Ball LM, Snijder P, van Zelderen-Bhola SL, Egeler RM. Diabetes insipidus in a child with a monosomy-7 associated myelodysplastic syndrome and neurofibromatosis I. Med Pediatr Oncol. 2003; 40:257–9.
crossref
24. Hoyt PR, Bartholomew C, Davis AJ, Yutzey K, Gamer LW, Potter SS, et al. The Evi1 proto-oncogene is required at midgestation for neural, heart, and paraxial mesenchyme development. Mech Dev. 1997; 65:55–70.
25. Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood. 1997; 90:2515–21.
crossref
26. Luckner G, Dunser MW, Jochberger S, Mayr VD, Wenzel V, Ulmer H, et al. Arginine vasopressin in 316 patients with advanced vasodilatory shock. Crit Care Med. 2005; 33:2659–66.
crossref

Fig. 1.
Karyotypes of the patients. (A) 45,XY,inv(3)(q21q26.2),-7[20] in patient 3. (B) 45,XX,t(3;3)(q21;q26.2),-7[25] in patient 4.
kjlm-27-133f1.tif
Table 1.
Hematological findings and karyotypes of the patients with 3q21q26 syndrome
Patient No. Age Sex FAB WBC (103/μL) Hb (g/dL) PLT (103/μL) LDH (U/L) BM blast (%) BM dysplasia Aberrant antigenic expression Karyotype
1 41 M AML M1 67,800 6.4 80K 467 91.2 No CD56 45,XY,inv(3)(q21q26.2),-7[8]
2 25 M AML M1 43,800 8.0 176K 702 81.2 No CD7 45,XY,inv(3)(q21q26.2),-7,inv(9)(p12q13)c[20]
3 49 M AML M2 30,500 10.1 232K 972 25.4 MK CD7, CD56 45,XY,inv(3)(q21q26.2),-7[20]
4 50 F AML M4 233,600 8.8 57K 5,432 81.0 MK, G, E CD7 45,XX,t(3;3)(q21;q26.2),-7[25]
5 27 M AML M7 4,600 10.1 275K 360 91.2 MK. G, E CD7, CD56 45,XY,inv(3)(q21q26.2),-7[19]/46XY[1]

Abbreviations: M, male; F, female; FAB, French-American-British; WBC, white blood cells; PLT, platelets; LD, lactate dehydrogenase; BM, bone marrow; MK, megakaryocytic lineage; G, granulocytic lineage; E, erythroid lineage.

Table 2.
Clinical course of the patients with 3q21q26 syndrome
Patient No. FAB Treatment Response Relapse OS (month) Current status (blast) Central DI
1 AML M1 AD No remission No 1.2 Alive pers (69.2%) No
2 AML M1 AD No remission No 2.0 Alive pers (74.0%) No
3 AML M2 AD→HDAC No remission No 2.7 Dead No
4 AML M4 AD→AI No remission No 6.5 Dead No
5 AML M7 AD→HDAC Hypocellular marrow (3 months) Yes 8.6 Dead Yes

Abbreviations: FAB, French-American-British; OS, overall survival; DI, diabetes insipidus; AD, AraC+Daunorubisin; AI, AraC+Idarubisin; HDAC, High dose Ara-C; Pers, persistence of bone marrow blasts.

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