Clinics and Pathology
Disease
T-cell acute lymphoblastic leukemia.
Phenotype stem cell origin
Lymphoblasts, either L1 or L2 in the FAB classification; mature T and myeloid markers variably co-expressed.
Epidemiology
Rare, approximately 10 cases described; evaluated to 2-5% of adult T-ALL ; not evaluated in childhood ALL; both sexes equally involved; found in children or young adults.
Clinics
No notable particular aspect.
Prognosis
Probably unfavorable, median survival below 18 months; improved by allogeneic bone marrow transplantation.
Cytogenetics
Cytogenetics morphological
In approximately 2/3 of cases; 2 cases with del(12p).
Cytogenetics molecular
Two BAC clones 290A12 and 118H17 (California Institute of Technology BAC library) encompasses all NUP98 gene and are split by translocation.
Variants
Not described.
Genes Involved and Proteins
Gene name
RAP1GDS1 (RAP1, GTP-GDP dissociation stimulator 1)
Location
4q23
Protein description
Somatic mutations
Not involved in other known clonal rearrangement associated with tumoral proliferation.
Gene name
NUP98 (nucleoporin 98 kDa)
Location
11p15.4
Protein description
Nucleoporin 98, a 98 kDa component of the nuclear pore complex implicated in nucleo-cytoplasmic transport.
Somatic mutations
Involved in different types of acute myeloid leukemia, as fusion gene with HOX A9, DDX10, HOX D13, TOP1, PMX1 and LEDGF, resulting respectively from t(7;11)(p15;p15), inv(11)(p15q22), t(2;11)(q31;p15), t(11;20)(p15;q11), t(1;11)(q23;p15) and t(9;11)(p22;p15).
Result of the Chromosomal Anomaly
Description
NUP98 breakpoint in the intron between exons B and C; 5-part of NUP98 is fused in frame with the whole coding sequence of RAP1GDS1; fusion gene called NRG: 5-NUP-RAP1GDS1-3. Variant described with breakpoint in NUP98 before exon A.t(4;11) generates only one chimeric protein 5NUP98 -3RAP1GDS1 which contains a variable part of NUP98 and the totality of smgGDS except for the initial methionine.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 10477737 | 1999 | The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia. | 0 |
| 26004809 | 2015 | NUP98/11p15 translocations affect CD34+ cells in myeloid and T lymphoid leukemias. | 0 |
| 10929031 | 2000 | t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia. | 0 |
| 11325654 | 2001 | Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute lymphoblastic leukemia. | 0 |
| 16419055 | 2006 | Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene. | 0 |
| 17233820 | 2007 | Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12). | 0 |
| 12651265 | 2003 | A multiplex reverse transcriptase-polymerase chain reaction strategy for the diagnostic molecular screening of chimeric genes: a clinical evaluation on 170 patients with acute lymphoblastic leukemia. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11325654 | 2001 | Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute lymphoblastic leukemia. | Cimino G et al |
| 10477737 | 1999 | The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia. | Hussey DJ et al |
| 8402548 | 1993 | Mapping of the chromosome 11 breakpoint of the t(4;11)(q21;p14-15) translocation. | Kalatzis V et al |
| 10929031 | 2000 | t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia. | Mecucci C et al |
Summary
Fusion gene
NUP98/RAP1GDS1 NUP98 (11p15.4) RAP1GDS1 (4q23) M t(4;11)(q23;p15)|NUP98/RAP1GDS1 NUP98 (11p15.4) RAP1GDS1 (4q23) TIC
Note
The breakpoint on chromosome 4 must be relocated in 4q23, since RAP1GDS1 gene maps at 4q23, see the complete update of this paper at t(4;11)(q23;p15) ..
t(4;11)(q21;p15) G- banding - Courtesy Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at the Waisman Center
Citation
Franck Viguié
t(4;11)(q21;p15) NUP98/RAP1GDS1
Atlas Genet Cytogenet Oncol Haematol. 2002-07-01
Online version: http://atlasgeneticsoncology.org/haematological/1473/t(4
