t(1;3)(p36;q21) PSMD2/PRDM16 ???

2016-09-01 Jean-Loup Huret Affiliation

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr
2.Laboratory of Hematology, Robert Debré Hospital, Medical Faculty (UPRES EA 20-70-IFR 53 Biomolecules), 51092, Reims Cedex, France
3.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr

Clinics and Pathology

Disease

Myeloid lineage (MDS, AML, therapy related AML, 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 stem cell origin

of 39 cases, there were: 22 myelodysplastic syndromes (MDS) (17/22 transformed into refractory acute myeloid leukemia (AML) of -M1 or -M4 type), 8 de novo AML, 3 therapy-related MDS, 2 polycythemia vera, 1 essential thrombocythemia, 1 chronic myelogenous leukemia (CML), 1 multiple myeloma, 1 waldenstroms 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 AML, 20 mths in MDS

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 3 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 3 to RPN1 in the t(3;3)(q21;q26) and 5 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.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
4063525	1985	Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia.	Bitter MA et al
4063527	1985	t(1;3)(p36;q21) in acute nonlymphocytic leukemia: a new cytogenetic-clinicopathologic association.	Bloomfield CD et al
8435325	1993	Clinical, haematological and cytogenetic features in 24 patients with structural rearrangements of the Q arm of chromosome 3.	Grigg AP et al
9632640	1998	The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression.	Huang S et al
1458454	1992	Acute leukemia with t(1;3)(p36;q21), evolution to t(1;3)(p36;q21), t(14;17)(q32;q21), and loss of red cell A and Le(b) antigens.	Marsden KA et al
11050005	2000	A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells.	Mochizuki N et al
6743828	1984	A new translocation, t(1;3) (p36;q21), in myelodysplastic disorders.	Moir DJ et al
8547101	1995	Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study.	Secker-Walker LM et al
10679911	2000	Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21).	Shimizu S et al
3476187	1987	Diagnostic and prognostic significance of t(1;3)(p36;q21) in the disorders of hematopoiesis.	Welborn JL et al

Summary

Note

This entity probably does not exist:
1- PSMD2 sits in 3q27, while the breakpoint is in 3q21;
2- PSMD2, a protein of the proteasome is well known by its alias, RPN1, while the true RPN1, a protein involved in N-glycosylation, sitting in 3q21, is better known by its full name: Ribophorin I.
The translocation is therefore likely to be t(1;3)(p36;q21) RPN1/PRDM16

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)