Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas of Genetics and Cytogenetics in Oncology and HaematologyCASE REPORTS in HAEMATOLOGY(Paper co-edited with the European LeukemiaNet)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 AdhvaryuClinicsAge and sex : 57 year(s) old female patient.Previous History : no preleukemiano previous malignant diseaseno inborn condition of noteOrganomegaly : no hepatomegaly ; no splenomegaly ; no central nervous system involvementBloodWBC : 34.1; Absolute lymphocyte count = 28,244 x 109/L. The lymphocytes were smal and mature in appearance. Rare (less than 1%) prolymphocytes were present. x 109/l; Hb : 13.2 g/dl; platelets : 187 x 109/l; Cyto pathology classificationCytology : Chronic lymphocytic leukemia/Smal 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/Smal lymphocytic lymphoma. SurvivalDate of 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 dateComplete remission : NoneTreatment related death : -Relapse : N/AStatus : Alive 04-2007KaryotypeSample : Bone marrow ; culture time : 24 h, , 48 and 72 hours ; banding : GTW (G-banding by Trypsin treatment fol owed 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 at relapse : N/AOther molecular cytogenetics 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.Other molecular cytogenetics 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 molecular studiestechnics : FISH studies on metaphases using LSI IGH break apart probes.results : FISH analysis confirmed the t(1;14;6)(q21;q32;p21).Other findingsAtlas Genet Cytogenet Oncol Haematol 2008; 4 664results : N/AA representative metaphase showing t(1;14;6) (q21;q32;p21) and other anomalies.A representative metaphase of PHA stimulated blood culture showing t(8;10) (p12;q22) as the constitutional abnormality.Atlas Genet Cytogenet Oncol Haematol 2008; 4 6653a: A representative FISH result showing a normal signal pattern of ATM and p53 loci (ATM loci labeled with Spectrum Green and p53 loci labeled with Spectrum Orange). 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 Genet Cytogenet Oncol Haematol 2008; 4 666A 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).CommentsCLL is primarily a B-cel disease represented with the fol owing 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% cel s, 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 collaborationSiddharth 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 .Internal linksAtlas Cardt(6;14)(p21;q32)A novel chromosomal translocation (6;14) (p22;q32) in a case of precursor B-cel Acute Case ReportLymphoblastic LeukemiaBibliographyGenomic aberrations and survival in chronic lymphocytic leukemia.Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bul inger L, Dohner K, Bentz M, Lichter PThe New England journal of medicine. 2000 ; 343 (26) : 1910-1916.PMID 11136261 Chronic lymphocytic leukemia.Chiorazzi N, Rai KR, Ferrarini MThe New England journal of medicine. 2005 ; 352 (8) : 804-815.PMID 15728813 Chronic Lymphocytic Leukemia (CLL).Reddy KSAtlas Genet Cytogenet Oncol Haematol.May (numero 2005). A novel chromosomal translocation (6;14) (p22;q32) in a case of precursor B-cell Acute Lymphoblastic leukemia.Adhvaryu SG, Dwivedi A, Stol PAtlas Genet Cytogenet Oncol Haematol.. Contributor(s)Written08-2007 Alka Dwivedi, Thomas Casey, Siddharth G AdhvaryuCitationThis paper should be referenced as such : Dwivedi A, Casey T, Adhvaryu SG . 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. August 2007 .URL : http://AtlasGeneticsOncology.org/Reports/0614AdhvaryuID100033.html© Atlas of Genetics and Cytogenetics in Oncology and HaematologyAtlas Genet Cytogenet Oncol Haematol 2008; 4 667Document Outline