t(X;10)(p11;p12) DDX3X/MLLT10
2016-11-01 Tatiana Gindina Affiliation1.Gorbacheva Research Institute of Pediatric Oncology Hematology and Transplantation at First Saint-Petersburg State Medical University named I.P.Pavlov, Saint-Petersburg, Russia / [email protected]
Abstract
Review on t(X;10)( p11;p12), with data on clinics and the genes involved.
Clinics and Pathology
Disease
T-Acute lymphoblastic leukemia/lymphoma
Phenotype stem cell origin
In two cases T-ALL was arrested at cortical stage. In the other 3 patients, immunophenotype was incomplete or not available [Brandimarte et al, 2013, 2014].
Epidemiology
t(X;10)( p11;p12) DDX3X/MLLT10 occurs in approximately 3% of adult T-ALL and characterizes a subgroup of NOTCH1 positive leukemias.
All five T- ALL patients were males aged 11 - 38 years (median 24.4 years).
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All five T- ALL patients were males aged 11 - 38 years (median 24.4 years).
| Pts | Age, gender | WBC (x109/l) | Immuno-phenotype | Karyotype | CI-FISH | Therapy | Follow up (months) |
| 1 | 11, M | 152.8 | Cortical T-ALL | n.a. | Split: MLLT10/10p12 Loss: PAX5, CDKN2A/B, Jak2/9p13-24 Gain: RP11-501C14/17q21.31 | AIEOP LLA 2000 | +73 alive [Brandimarte et al, 2013] |
| 2 | 26, M | 88 | Cortical: CD45+, cyCD3+, TDT+, sCD3+, CD4+, CD5+, CD38+, CD1a+, CD34-, CD10- | 46,Y,t(X;10)(p11;p12),add(1)(p36),del(9)(p11p24)[10]/ 46,idem,del(6)(q15)[1]/ 46,XY[11] | del(5q)/MAPK9,FLT4 del(6)(q15)/CASP8AP2 del(9)(p21)/CDKN2A/B | GIMEMA 0904 HLA identical SCT | +80 alive [Brandimarte et al, 2014] |
| 3 | 38, M | 160 | TDT+, CD7+, cyCD3+, CD5+, CD4+, CD8- | n.a. | del(9)(p21)/CDKN2A/B | GIMEMA 0904 | Relapse +38 dead [Brandimarte et al, 2014] |
| 4 | 31, M | 700 | n.a. | 46,XY[20] | normal | GIMEMA 0904 | Relapse +10 dead [Brandimarte et al, 2014] |
| 5 | 16, M | 68 | CD45+, TDT+, HLA-DR+, CD7+, CD2+, sCD3+, CD5+, CD8+, CD19-, CD14-, CD13-, CD33-, CD34-, CD22-, CD20-, CD4- | 46,XY[20] | del(9)(p21)/CDKN2A | GIMEMA 0496 unrelated SCT | Relapse +42 dead [Brandimarte et al, 2014] |
Treatment
All patients achieved hematologic remission but 3 relapsed and died. Two patients are alive, one of them was treated by HLA identical Hematopoietic stem cell transplantation (HSCT).
Genes Involved and Proteins
Gene name
DDX3X (DEAD-box helicase 3, X-linked)
Location
Xp11.4
Protein description
DDX3X is a member of the large family of RNA helicases with a DEAD box domain that is involved in RNA transcription, splicing, mRNA transport, translation initiation, and cell-cycle regulation [Rosner et al, 2007].
Somatic mutations
DDX3X somatic mutations have recently been discovered in medulloblastoma, chronic lymphocytic leukemia, and Burkitt lymphoma. Recurrent DDX3X homozygous deletions were identified in gingivobuccal oral squamous cell carcinoma [Brandimarte L., et al, 2013].
Gene name
MLLT10 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10)
Location
10p12.31
Protein description
MLLT10 contains 3 Zn fingers and a leucine zipper; nuclear localisation; transcription factor [Morerio and Panarello, 2005]
Result of the Chromosomal Anomaly
Oncogenesis
DDX3X is one of the genes that escapes X-inactivation in females [Lahn B.T. et al., 1997]. As all patients with DDX3X-MLLT10 positive T-ALL were males, no wild-type DDX3X allele was retained in the leukemic blasts, suggesting that the complete absence of a normally functional DDX3X protein might contribute to leukemogenesis. DDX3X appeared to have oncogenic as well as tumor supressor functions [Change P.C. et al., 2006; Botlagunta M. et al., 2008; Brandimarte L., et al, 2014].
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36158701 | 2022 | Broad genomic workup including optical genome mapping uncovers a DDX3X: MLLT10 gene fusion in acute myeloid leukemia. | 53 |
| 32843425 | 2020 | Failure of tofacitinib to achieve an objective response in a DDX3X-MLLT10 T-lymphoblastic leukemia with activating JAK3 mutations. | 45 |
| 38102963 | 2024 | Challenging our understanding of B-cell lymphomagenesis and risk: Paediatric high-grade B-cell lymphoma, not otherwise specified with a DDX3X::MLLT10 fusion and an IGH deletion. | 28 |
| 24584351 | 2014 | DDX3X-MLLT10 fusion in adults with NOTCH1 positive T-cell acute lymphoblastic leukemia. | 16 |
| 23673860 | 2013 | New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia. | 0 |
| 36000950 | 2022 | Diverse mutations and structural variations contribute to Notch signaling deregulation in paediatric T-cell lymphoblastic lymphoma. | 0 |
| 30347268 | 2019 | Clinical Evaluation of Massively Parallel RNA Sequencing for Detecting Recurrent Gene Fusions in Hematologic Malignancies. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9381176 | 1997 | Functional coherence of the human Y chromosome. | Lahn BT et al |
Summary
Fusion gene
DDX3X/MLLT10
Citation
Tatiana Gindina
t(X;10)(p11;p12) DDX3X/MLLT10
Atlas Genet Cytogenet Oncol Haematol. 2016-11-01
Online version: http://atlasgeneticsoncology.org/haematological/1701/t(x
