T-cell acute lymphoblastic leukemia with t(7;14)(p15;q11.2)/HOXA-TCRA/D and biallelic deletion of CDKN2A. Case report and literature review

Jonathon Mahlow, Salah Ebrahim, Anwar N Mohamed  

Cytogenetics Laboratory, Pathology Department, Wayne State University School of Medicine and Detroit Medical Center, Detroit MI, USA

Previous history

Preleukaemia
-
Malignant disease
-
Inborn condition
-
Main items
-
Note
Family History: Negative for cancer

Clinics case report

Age
9 yrs
Sex
M
Liver
-
Spleen
+
Lymph nodes
+
Cns involv
-
Note
Positive for splenomegaly, bilateral enlarged kidneys, large mediastinal mass, extensive lymphadenopathy of intrathoracic, retroperitoneal, cervical, and axillary regions. Cerebral spinal fluid negative for malignant cells.

Blood data

Wbc
31.6
Hb
8.6
Platelets
15
Blasts
65
Bone marrow
Dry tap
Note
Peripheral blood showed anemia, thrombocytopenia and leukocytosis.

Cyto path

Cytology
Peripheral blood smear showed large L2 lymphoblasts with nucleoli, normochromic, normocytic RBCs and markedly decreased platelets.
Immunophenotype
Flow cytometric analysis of peripheral blood demonstrated an abnormal CD45dim circulating lymphoblasts (75%) expressing CD2, CD5, CD7, CD8, CD10, cytoplasmic CD3, TdT and partially expressing weak CD30. Overall, these findings were consistent with T-cell malignancy.
Rearranged ig tcr
No rearrangements of TCRB and TCRA/D genes by FISH.
Electron microscopy
Not performed.
Precise diagnosis
T-cell acute lymphoblastic leukemia (T-ALL).

Survival data

Date diagnosis
09-2013
Treatment
Patient was treated with COG-AALL00434 protocol including vincristine, daunorubicin hydrochloride, prednisone, pegaspargase, and intrathecal cytarabine and methotrexate.
Complete remission
+
Treatment relat death
-
Relapse
-
Status
A
Date last follow
01-2014
Survival
4
Note
In remission; on maintenance chemotherapy as of Jan 28, 2014.

Karyotype

Sample
Peripheral blood
Culture time
24 and 48hrs unstimulated cultures
Banding
GTG
Results
46, XY,del(6)(q14q21),t(7;14)(p15;q11.2),del(9)(p13)[12]/92,idemx2,[7]/46,XY[1] (Figure 1)
Mol cytogenet technics
The aCGH revealed a 33.3Mb terminal monoallelic deletion of chromosome 9p13.3->pter, with 1.39 Mb biallelic deletions in the 9p21.3 region which spans the CDKN2A gene locus (Figure 4). It also detected a large 20.7 Mb interstitial deletion at del(6)(q14.1q16.2) and 1.34 Mb duplication within the 4q32.1 region.

Images

Atlas Image
Figure 1: G-banded karyotype of the pseudodiploid cell line demonstrating del(6q) (hollow arrow), t(7;14)(p15;q11.2) (thin arrows), and del(9p) (solid arrow).
Atlas Image
Figure 2: FISH was performed using CDKN2A (orange) and the control CEP 9 (green) DNA probe set. The hybridization revealed biallelic loss of CDKN2A in an abnormal metaphase (long arrow) while the normal diploid interphase cell had two copies of each (short arrow).
Atlas Image
Figure 3: FISH of a t(7;14) carrying metaphase cell demonstrating fusion of HOXA-TCRA/D gene regions (thin arrow).
Atlas Image
Figure 4: aCGH plot for chromosome 9 showing compound deletions. The light blue region indicates a terminal monoallelic deletion of 33.3 Mb of 9p while dark blue region points to biallelic deletion within the 9p21.3.

Comments section

Comments
In summary, the t(7;14)(p15;q11.2) translocation is extremely rare resulting in an aberrant juxtaposing of HOXA-TCRD genes. Therefore, TCRD/14q11.2 may consider as a new variant partner for activation of HOXA/7p15 in T-ALL. Although the expression of HOXA genes was not tested in the present case, we assume it was upregulated as documented previously in HOXA-TCRD case and HOXA-TCRB cases.

Bibliography

Pubmed IDLast YearTitleAuthors

Citation

Jonathon Mahlow, Salah Ebrahim, Anwar N Mohamed

T-cell acute lymphoblastic leukemia with t(7;14)(p15;q11.2)/HOXA-TCRA/D and biallelic deletion of CDKN2A. Case report and literature review

Atlas Genet Cytogenet Oncol Haematol. 2014-01-01

Online version: http://atlasgeneticsoncology.org/case-report/208873/js/lib/gene-fusions-explorer/