A case of Chronic Lymphocytic Leukemia (CLL) with a rare chromosome abnormality: t(1;14;6)(q21;q32;p21), a variant of t(6;14)(p21;q32).

Alka Dwivedi, Thomas Casey, Siddharth G Adhvaryu  

Cinical and Molecular Cytogenetics Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229-3900, USA (AD)(SGA); Brooke Army Medical Center, Fort Sam Huston, San Antonio, Texas, USA (TC)

Previous history

Preleukaemia
-
Malignant disease
-
Inborn condition
-
Main items
N/A

Clinics case report

Age
57 yrs
Sex
F
Liver
-
Spleen
-
Lymph nodes
Scattered, mildly enlarged nodes (axilla, mediastinum, retroperitoneum and pelvis).
Cns involv
-

Blood data

Wbc
34.1; Absolute lymphocyte count = 28,244 x 109/L. The lymphocytes were small and mature in appearance. Rare (less than 1%) prolymphocytes were present.
Hb
13.2
Platelets
187
Blasts
0
Bone marrow
Variably cellular, areas of aplasia alternating with areas of residual hematopoiesis with 40% cellularity. The cellular areas show an interstitial lymphoid infiltrate comprised of small mature appearing lymphocytes with rare prolymphocytes. No clusters of large lymphocytes are present. No evidence of large cell or prolymphocytic transformation.

Cyto path

Cytology
Chronic lymphocytic leukemia/Small lymphocytic lymphoma.
Immunophenotype
Bone marrow 05/09/07: CD5+, CD19+, CD20+(dim), CD22+(very dim), CD23+, CD38+, HLA-DR+, surface lambda+(dim), ZAP-70+, CD10-. Matutes score =4 of 5.
Pathology
See bone marrow above.
Electron microscopy
Not performed.
Precise diagnosis
Chronic lymphocytic leukemia/Small lymphocytic lymphoma.

Survival data

Date diagnosis
06-2005; Original diagnosis made by flow cytometric analysis of peripheral blood on 06/2005. First bone marrow with cytogenetic analysis performed on 05/2007.
Treatment
None to date
Complete remission
N/A
Treatment relat death
-
Relapse
N/A
Status
A
Date last follow
04-2007

Karyotype

Sample
Bone marrow
Culture time
24, 48 and 72 hours
Banding
GTW (G-banding by Trypsin treatment followed by Wright stain).
Results
46,XX,t(8;10)(p21;q22)c[16]/46,idem,t(1;14;6)(q21;q32;p21),-6,-12,+1-2mar [4]
Karyotype relapse
N/A
Mol cytogenet technics
Fluorescence In Situ Hybridization (FISH) using Vysis LSI IGH break apart (Cat # 32-191019) on the mataphases, CLL I probe set (LSI ATM/p53) and CLL II probe sets (CEP 12/CEP13q14.3/CEP13q34 probes) (Cat # 32-191025) on interphase nuclei.
Mol cytogenet results
2. FISH analysis (Fig. 4) of IGH break-apart probe on G-banded metaphases (Fig. 1) showed the complex translocation, t(1;14;6)(q21;q32;p21). The LSI IgH 3 flanking region (250 kb) is labeled with Spectrum Orange and LSI IgH V 5 region (900 kb) is labeled with Spectrum Green. A normal fusion signal is seen on chromosome 14. A translocation between 14q32 and 6p21 led to the IgH signal being split with der(14) retaining the IgH 3 flanking region (red) and translocation of 5 IgH V region (green) to der (6). Subsequent complex translocations involving chromosomes 1, 14 and 6 are evident by der(14) and der (1) harboring the 1q and 6p regions, respectively.

Other molec studies

Technics
FISH studies on metaphases using LSI IGH break apart probes.
Results
FISH analysis confirmed the t(1;14;6)(q21;q32;p21).

Other findings

Note
N/A

Images

Atlas Image
A representative metaphase showing t(1;14;6) (q21;q32;p21) and other anomalies.
Atlas Image
A representative metaphase of PHA stimulated blood culture showing t(8;10) (p12;q22) as the constitutional abnormality.
Atlas Image
3b: A representative FISH result showing a deletion of 13 (q34) (CEP 12, 13 (q14.3) and 13 (q34) labeled with Spectrums Orange, Green and Aqua, respectively).
Atlas Image
A representative FISH result confirming the variant t(1;14;6) (q21;q32;p21) using the IGH break apart probe (entire IGH variable region (900kb) labeled with Spectrum Green and IGH 3 flanking region (250 kb) labeled with Spectrum Orange). A normal fusion signal (yellow) is seen on chromosome 14. Abnormal signal pattern for this probe is seen on der (14) retaining the 3 IgH flanking region and translocation of 5 IGH V region to der (6).

Comments section

Comments
CLL is primarily a B-cell disease represented with the following anomalies; +12, del(11q) and del(17p). Cases of CLL with 14q32 (IGH) rearrangements have been reported. We present here a unique case of CLL showing a variant CCND3:IGH rearrangement in the form of t(1;14;6)(q21;q32;p21). The loss of 6q (indicated by -6) has been reported in CLL. Exact significance of monosomy 12 is not known. Interphase FISH showed del(13)(q34) in 10% cells, the significance of which is not known (Fig 3). Metaphase FISH performed with the LSI IGH break apart probe confirmed the t(1;14;6) (Fig 4).This case does not show the common deletions ( 6q, 13q14.3, 11q22-23 or 17p13) or amplification (trisomy 12).
Call for collab
Siddharth G Adhvaryu, Ph.D., FACMG, Clinical and Molecular Cytogenetics Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas-78229, USA; Corresponding Author: Dr Siddharth G Adhvaryu; E mail: ADHVARYU@UTHSCSA.EDU .

Bibliography

Pubmed IDLast YearTitleAuthors
111362612000Genomic aberrations and survival in chronic lymphocytic leukemia.Döhner H et al
157288132005Chronic lymphocytic leukemia.Chiorazzi N et al

Citation

Alka Dwivedi, Thomas Casey, Siddharth G Adhvaryu

A case of Chronic Lymphocytic Leukemia (CLL) with a rare chromosome abnormality: t(1;14;6)(q21;q32;p21), a variant of t(6;14)(p21;q32).

Atlas Genet Cytogenet Oncol Haematol. 2007-08-01

Online version: http://atlasgeneticsoncology.org/case-report/208831/a-case-of-chronic-lymphocytic-leukemia-(cll)-with-a-rare-chromosome-abnormality-t(1;14;6)(q21;q32;p21)-a-variant-of-t(6;14)(p21;q32)