t(X;10)(p11;p12) DDX3X/MLLT10

2016-11-01   Tatiana Gindina 

1.Gorbacheva Research Institute of Pediatric Oncology Hematology and Transplantation at First Saint-Petersburg State Medical University named I.P.Pavlov, Saint-Petersburg, Russia / tatgindina@gmail.com

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).
PtsAge, genderWBC
(x109/l)
Immuno-phenotypeKaryotypeCI-FISHTherapyFollow up (months)
111, M152.8Cortical T-ALLn.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]
226, M88Cortical: 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]
338, M160TDT+, CD7+, cyCD3+, CD5+, CD4+, CD8-n.a.del(9)(p21)/CDKN2A/BGIMEMA 0904Relapse +38 dead
[Brandimarte et al, 2014]
431, M700n.a.46,XY[20]normalGIMEMA 0904Relapse +10 dead [Brandimarte et al, 2014]
516, M68CD45+, TDT+, HLA-DR+, CD7+, CD2+, sCD3+, CD5+, CD8+, CD19-, CD14-, CD13-, CD33-, CD34-, CD22-, CD20-, CD4-46,XY[20]del(9)(p21)/CDKN2AGIMEMA 0496 unrelated SCTRelapse +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 IDYearTitleCitations
236738602013New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia.25
245843512014DDX3X-MLLT10 fusion in adults with NOTCH1 positive T-cell acute lymphoblastic leukemia.11
303472682019Clinical Evaluation of Massively Parallel RNA Sequencing for Detecting Recurrent Gene Fusions in Hematologic Malignancies.7
328434252020Failure of tofacitinib to achieve an objective response in a DDX3X-MLLT10 T-lymphoblastic leukemia with activating JAK3 mutations.2
360009502022Diverse mutations and structural variations contribute to Notch signaling deregulation in paediatric T-cell lymphoblastic lymphoma.0

Bibliography

Pubmed IDLast YearTitleAuthors
93811761997Functional 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;10)(p11;p12)

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