t(1;3)(p36;q21)

Identity

	t(1;3)(p36;q21) G-banding (left) - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, UW Cytogenetic Services; R-banding (right) Courtesy Pascale Cornillet-Lefebvre and Stéphanie Struski (above) and Christiane Charrin (below)

Clinics and Pathology

Disease	Myeloid lineage (MDS, ANLL, therapy related ANLL, CML, MPD); features similar to those of the 3q21q26 syndrome including normal or elevated platelet count at diagnosis, megakaryocytic hyperplasia and dysplasia. Very rarely in lymphoid lineage
Phenotype / cell stem origin	of 39 cases, there were: 22 myelodysplastic syndromes (MDS) (17/22 transformed into refractory acute non lymphoblastic leukemia (ANLL) of -M1 or -M4 type), 8 de novo ANLL, 3 therapy-related MDS, 2 polycythemia vera, 1 essential thrombocythemia, 1 chronic myelogenous leukemia (CML), 1 multiple myeloma, 1 waldenstrom's macroglobulinemia
Epidemiology	patients are aged: 30-80 yrs
Clinics	Roughly 50% of patients present with MDS, another 10% with therapy associated MDS, 25% with de novo AML, and the remainder with a range of other myeloproliferative disorders. The majority of MDS patients transform into AML with a short preleukemic phase. Blood data: frequent thrombocytosis or normal platelet count
Cytology	frequently characterized by dysmegakaryocytopoiesis
Pathology	The pathology is typical of MDS, often with a prominent monocytic component. Trilineage dysplasia. Acute leukemias that evolve usually show the morphology of M4 AML.
Treatment	Patients are treated with conventional chemotherapy for AML.
Prognosis	Very poor so far: from 16 cases, median survival was 6 mths in ANLL, 20 mths in MDS

Cytogenetics

Note	Other rearrangements showing similar clinical features include inv(3)(q21q26), t(3;3)(q21;q26), t(3;5)(q21;q31), t(3;8)(q21;q24), and t(3;21)(q26;q22). The breakpoints in 3q21 cluster in a 50 kb region centromeric to the breakpoint in inv(3)(q21;q26) and the ribophorin gene (RPN1). The breakpoints at 1p36 are clustered in a 90 kb region at 1p36.3.
Additional anomalies	del (5q) in 5 of 20 cases (1/4)

Genes involved and Proteins

Note

Mechanisms of Oncogenesis : The available data suggest that transcription of MEL1 (MDS1/EVI1 -like gene) is activated as a result of translocation bringing the gene just 3Õ to RPN1 gene at 3q21. MEL1 is a 1257 amino acid protein that is homologous (63% similar in amino acid sequence) to EVI. The mechanism of activation of MEL1 is similar to EVI1 that is activated by juxtaposition 3Õ to RPN1 in the t(3;3)(q21;q26) and 5Õ to RPN1 in the inv(3)(q2126). It appears that MEL1 is normally expressed in uterus and kidney and not in normal hematopoietic cells or in leukemias that lack the t(1;3)(p36;q31 The MEL1 protein contains 2 DNA binding domains (7 C2H2 zinc finger repeats at the amino terminus and 3 zinc finger repeats at the carboxyl terminus). The amino terminal domain of MEL1 contains a PRD domain, a motif also found in the same location in the MDS1/EV1 protein but not in MDS1). This is of interest because this domain is also found in RIZ, PRDI-BF1, and egl-43 and is homologous to the SET (Suvar3-9, Enhancer of zeste, Trithorax) domain that present in MLL. Inclusion of this domain in EVI1 appears to convert EVI1 from a transcriptional repressor to an activator. Therefore MEL1 may be a transcriptional activator. The target genes of MEL1 have not been identified.

External links

Other database	t(1;3)(p36;q21)	Mitelman database (CGAP - NCBI)
Other database	t(1;3)(p36;q21)	CancerChromosomes (NCBI)

Bibliography

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Contributor(s)

Written	08-1997	Jean-Loup Huret
		Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated	11-2000	Pascale Cornillet-Lefebvre, Sylvie Daliphard, Stéphanie Struski
		Laboratory of Hematology, Robert Debré Hospital and Medical Faculty (UPRES EA 20-70-IFR 53 Biomolecules), 51092, Reims Cedex, France
Updated	05-2002	Jay L Hess
		Department of Pathology, The University of Michigan, M5240 Medical Science I, 1301 Catherine Avenue, Ann Arbor, MI 48109-0602, USA

Citation

This paper should be referenced as such :

Huret JL . t(1;3)(p36;q21). Atlas Genet Cytogenet Oncol Haematol. August 1997 . URL : http://AtlasGeneticsOncology.org/Genes/t0103.html

Cornillet-Lefebvre P, Daliphard S, Struski S . t(1;3)(p36;q21). Atlas Genet Cytogenet Oncol Haematol. November 2000 . URL : http://AtlasGeneticsOncology.org/Genes/t0103.html

Hess JL . t(1;3)(p36;q21). Atlas Genet Cytogenet Oncol Haematol. May 2002 . URL : http://AtlasGeneticsOncology.org/Genes/t0103.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Sep 24 21:06:07 2008

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