An adult case of biphenotypic acute leukemia with t(6;14)(q25;q32)

S Toyotaka Kawamata, Miho Ogawa, Tomomi Takei, Reina Takeda, Kiyosumi Ochi, Kazuaki Yokoyama, Tomofusa Fukuyama, Nobuhiro Ohno, Kaoru Uchimaru, Arinobu Tojo  

Department of Hematology/Oncology, Research Hospital (KT, OM, TT, TR, OK, YK, FT, ON, UK, TA); Division of Cell Therapy, Advanced Clinical Research Center (TF); Division of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, the University of Tokyo (TA), 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Toyotaka Kawamata: toyotaka@ims.u-tokyo.ac.jp, Miho Ogawa: miho.ogawa327@gmail.com; Tomomi Takei: t-takei@ims.u-tokyo.ac.jp; Reina Takeda: reina.takeda@gmail.com; Kiyosumi Ochi: equuleus2015@gmail.com; Kazuaki Yokoyama: k-yoko@ims.u-tokyo.ac.jp; Tomofusa Fukuyama: tfukuyam@ims.u-tokyo.ac.jp; Nobuhiro Ohno: nobuohno@ims.u-tokyo.ac.jp; Kaoru Uchimaru: uchimaru@ims.u-tokyo.ac.jp; Arinobu Tojo: a-tojo@ims.u-tokyo.ac.jp

Previous history

Preleukaemia
-
Malignant disease
-
Inborn condition
-

Clinics case report

Age
66 yrs
Sex
M
Liver
-
Spleen
+
Lymph nodes
+ Slightly enlarged lymph nodes (submental, cervical, axial, mediastinal, inguinal) were detected by computed tomography.
Cns involv
-

Blood data

Wbc
130.4
Hb
13.9
Platelets
40
Blasts
93
Bone marrow
Hypercellular marrow (NCC 497109/l) with 93.8% blast; monotonous and high nuclear-cytoplasm (N/C) ratio blast cells which had a cleaved nuclear were expanded.

Cyto path

Phenotype
Mixed phenotype acute leukaemia, T/myeloid, NOS
Immunophenotype
Positve for CD2,cyCD3,CD7,CD13,CD15,CD34,HLA-DR, and dimly positive for CD33,MPO,TdT. Negative for CD1a,CD5,CD11b,CD117,TCR-AB,TCR-GD
Rearranged ig tcr
Not performed.
Pathology
Acute leukemia compatible.
Electron microscopy
Not performed.
Precise diagnosis
Mixed phenotype acute leukemia, T/myeloid, NOS.

Survival data

Date diagnosis
04-2015
Treatment
Japan adult leukemia study group T-ALL213-O induction therapy including vincristine (VCR), cyclophosphamide (CPA), daunorubicin (DNR), L-Asparaginase (L-ASP) and Predonisolone (PSL).
Complete remission
+
Treatment relat death
-
Relapse
-
Status
A
Date last follow
09-2015
Survival
5

Karyotype

Sample
Bone marrow
Culture time
24-48
Banding
G-banding
Results
46,XY,t(6;14)(q25;q32) [20]
Karyotype relapse
not applicable
Mol cytogenet technics
fluorescence in situ hybridization(FISH) analysis using IgH 3 flanking region/V probes. 14q32 (IgH) break apart probe is a mixture of two probes, 3 IgH flanking probe and IgH variable region probe as shown in Figure 2a.
Mol cytogenet results
Negative for immunoglobulin heavy chain (IgH) translocation (Figure 2b).

Other molec studies

Technics
Polymerase chain reaction (PCR) and Sanger sequencing
Results
Positive for Flt3-internal tandem duplication(ITD). Negative for c-kit mutation.

Images

Atlas Image
Partial karyotype from bone marrow cells at the time of diagnosis showing the chromosomal translocation t(6;14)(q25;q32).
Atlas Image
FISH analysis was performed by LSI Medience (Tokyo, Japan). (a) A scheme of 3 flanking probe and V probe which is modified from the technical information of LSI Medience corporation (Tokyo, Japan) web site.(b)Negative result for IgH gene rearrangement in this case.

Comments section

Comments
We present an adult case of biphenotypic acute leukemia with t(6;14)(q25;q32). Chromosome translocations involving 14q32 are generally represented by B cell neoplasms, because the immunoglobulin heavy chain (IgH) gene is located in this region. However, BCL11B gene also located in 14q32 was shown to be involved in this translocation (Bezrookove et al.,2004). BCL11B, a member of the Kruppel family of zinc finger trascription factors, plays a critical role in T cell development and functions as a tumor suppressor (Wakabayashi et al.,2003). The partner gene of this translocation is unknown. The 28S ribosomal DNA (RN28S1) was reported as a candidate fusion partner (Kobayashi et al.,2014), but this gene is not located in 6q25. The phenotype of haematological malignancies with t(6;14)(q25;q32) is variable. These include acute lymphoblastic leukemia (ALL) (Heerema et al.,2002), mixed phenotype acute leukemia (Hayashi et al.,1990, Batanian et al.,1996, Georgy et al.,2008, Kobayashi et al.,2014), acute myeloid leukaemia (AML) (Raimondi et al.,1989, Bezrookove et al.,2004), chronic T cell neoplasm (Inwards et al.,1990) and chronic lymphocytic leukaemia (CLL) (Mayr et al.,2006). In 7 of 9 acute leukaemia cases with this translocation, both myeloid and T-cell lineage markers were detected. No immunophenotype was described in the remaining two cases. This translocation may affect expression of T-cell lineage marker, but the role of BCL11B is unclear.

Article Bibliography

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23999101990Cytogenetic findings in 21 cases of peripheral T-cell lymphoma.Inwards DJ et al
2364166199014q32 translocations are associated with mixed-lineage expression in childhood acute leukemia.Hayashi Y et al
87807431996Is t(6;14) a non-random translocation in childhood acute mixed lineage leukemia?Batanian JR et al
119204812002Abnormalities of chromosome bands 15q13-15 in childhood acute lymphoblastic leukemia.Heerema NA et al
125659052003Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas.Wakabayashi Y et al
127174332003Bcl11b is required for differentiation and survival of alphabeta T lymphocytes.Wakabayashi Y et al
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Citation

S Toyotaka Kawamata, Miho Ogawa, Tomomi Takei, Reina Takeda, Kiyosumi Ochi, Kazuaki Yokoyama, Tomofusa Fukuyama, Nobuhiro Ohno, Kaoru Uchimaru, Arinobu Tojo

An adult case of biphenotypic acute leukemia with t(6;14)(q25;q32)

Atlas Genet Cytogenet Oncol Haematol. 2015-09-01

Online version: http://atlasgeneticsoncology.org/case-report/208878/css/js/teaching-explorer/