T-cell acute lymphoblastic leukemia with t(4;11)(q23;p15) and NUP98/RAP1GDS1 gene fusion: Case report and review of literature

S Mohanad Deen, Anwar N. Mohamed  

Cytogenetics Laboratory, Pathology Department, Wayne State University School of Medicine, Detroit Medical Center, Detroit, MI USA. amohamed@dmc.org; mdeen@med.wayne.edu

Previous history

Preleukaemia
-
Malignant disease
-
Inborn condition
-

Clinics case report

Age
15 yrs
Sex
M
Liver
-
Spleen
-
Lymph nodes
+ Significant lymphadenopathy involving bilateral cervical, posterior auricular, submandibular, supraclavicular, and inguinal lymph nodes.
Cns involv
-

Blood data

Wbc
72.8
Hb
9.4
Platelets
72
Blasts
94
Bone marrow
Hypercellular with near-replacement with L2 lymphoblasts.
Note
Serum chemistries were significant for LDH of 923 U/L and uric acid of 7.8 mg/dL.

Cyto path

Phenotype
T-cell acute lymphoblastic leukemia (T-ALL).
Immunophenotype
Flowcytometry of bone marrow aspirate revealed a predominant abnormal CD45 dim lymphoblasts population (97%) expressing CD3, CD5, CD7, CD10, TdT, cytoplasmic CD3, thymic associated marker CD1a, and partial expression of CD8, CD2, and CD30 antigens.
Rearranged ig tcr
not performed.
Electron microscopy
not performed.
Precise diagnosis
T-cell acute lymphoblastic leukemia of thymic origin.

Survival data

Date diagnosis
05-2015
Treatment
Patient started chemotherapy on May 15th with vincristine, bortezomib, and daunorubicin. Three days later, he received PEG-asparaginase. On Day 29, bone marrow evaluation revealed morphologic and cytogenetic remissions. The minimal residual disease (MRD) was negative (<0.01%), therefore the leukemia was classified as standard risk.
Complete remission
+ Complete remission was obtained.
Treatment relat death
-
Relapse
-
Status
A
Date last follow
12-2015
Survival
7 +

Karyotype

Sample
Bone marrow
Culture time
24 and 48h with 10% GCT.
Banding
GTG
Results
46,XY,t(4;11)(q23;p15),del(9)(p13)[20] (Figure 1).
Mol cytogenet results
In addition, we investigated RAP1GDS1 and NUP98 as candidate genes for the t(4;11)(q23;p15) breakpoints. FISH using two differentially labeled DNA probes was performed. The BAC RP11-64A22/4q23 covering the centromeric portion of RAP1GDS1 gene locus was labeled green, while the RP11-348A20/11p15.4 covering NUP98 gene locus was labeled orange (BlueGnome, Illumina Cambridge UK). The hybridization revealed a dual fusion signals on the der(4) and der(11) chromosomes (Figure 2). These results indicated that the t(4;11)(q23;p15) fused the NUP98 gene with RAP1GDS1.

Images

Atlas Image
Figure 1: G-banded karyotype showing an apparently balanced t(4;11)(q23;p15) [arrows], and deleted 9p.
Atlas Image
Figure 2: Dual color FISH on a metaphase with t(4;11)(q23;p15) using the DNA probes BAC RP11-348A20/11p15.4 and RP11-64A22/4q23 showing a dual fusion signals hybridized on der(4) and der(11) (arrows) while the green signal and orange signal on normal chromosomes 11 and 4, respectively.

Comments section

Comments

Bibliography

Pubmed IDLast YearTitleAuthors
219482992011NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights.Gough SM et al
104777371999The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia.Hussey DJ et al
109290312000t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia.Mecucci C et al
113256542001Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute lymphoblastic leukemia.Cimino G et al
164190552006Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene.van Zutven LJ et al

Citation

S Mohanad Deen, Anwar N. Mohamed

T-cell acute lymphoblastic leukemia with t(4;11)(q23;p15) and NUP98/RAP1GDS1 gene fusion: Case report and review of literature

Atlas Genet Cytogenet Oncol Haematol. 2015-12-01

Online version: http://atlasgeneticsoncology.org/case-report/208881/t-cell-acute-lymphoblastic-leukemia-with-t(4;11)(q23;p15)-and-nup98-rap1gds1-gene-fusion-case-report-and-review-of-literature