Blood, Vol. 92 No. 4 (August 15), 1998:
pp. 1454-1455
CORRESPONDENCE
A Unique Translocation of the TEL Gene in a Case of Acute
Myelogenous Leukemia With inv(12)(p13q15)
 |
LETTER |
To the Editor:
Chromosome band 12p13 is known as a recurring site for cytogenetic
alteration in a variety of hematological malignancies such as acute
lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), and
myelodysplastic syndrome (MDS).1 Recently, the TEL gene has
been shown to be involved in hematological malignancies with 12p13
aberration, most of which exhibit reciprocal translocation between
12p13 and various partner loci, including 3q26, 5q33, 9q34, 21q22, and
22q11. By 12p13 translocation, the TEL gene is disrupted and fused to
its partner genes such as PDGFR-
,2 ABL,3 and
AML-1.4 On the other hand, invesion 12 at p13 is a rare
abnormality and only 9 cases (1 AML and 8 MDS) were reported
previously.5-8 Whether the TEL gene is involved in this aberration has not been determined. We describe here an additional case
of AML with inv(12)(p13q15) in which the rearrangement of the TEL gene
was demonstrated by fluorescence in situ hybridization (FISH).
A 59-year-old woman was referred to our hospital because of marked
leukocytosis associated with pharyngitis in April 1995. Until then, she
had no history of abnormal hematological data in a routine check-up. On
admission, hepatosplenomegaly was pointed out and her white blood cell
count was 127 × 109/L with 90% of blasts, which were
positive for myeloperoxidase and ASD-chrolo-acetate. The morphology of
the blasts was compatible with FAB-M2. Surface markers were positive
for CD33 and weakly positive for CD7, CD13, and HLA-DR. Bone marrow
aspiration proved dry tap, but a biopsy specimen showed hypercellular
marrow with diffuse and severe myelofibrosis. The karyotype analysis of
peripheral blasts showed a main clone with 48 XX, add(6)(q27), +8,
inv(12)(p13q15), add(15)(q25), +add(15)(q25) (Fig
1). The patient was diagnosed as AML-M2 and
then received two courses of induction therapy with behenoyl
arabinosylcytosine, daunorubicin, 6-mercaptopurine, and prednisone, but
could not achieve remission. The further salvage therapy with cytosine
arabinoside, etoposide, predonisone, and mitoxantrone also resulted in
treatment failure. She died of multiple organ failure in August 1995, and autopsy specimens disclosed massive infiltration of leukemia cells
in spleen, liver, lungs, brain, kidneys, adrenal glands, stomach,
colon, skin, pharynx, tonsil, and systemic lymph nodes.
View larger version (19K):
[in this window]
[in a new window]
| Fig 1.
G-banded karyotypes of a leukemia cell. Structurally
abnormal or additional chromosomes are shown by arrows.
|
|
Southern blot hybridization was performed on blast cells using two
kinds of TEL cDNA probes corresponding to exon 2 and 3 of the
gene,2,9 respectively. After EcoRI and
HindIII digestion, the patient sample did not show any
rearranged bands (data not shown). Next, FISH analysis was performed
with a yeast artificial chromosome (YAC 964c10).1 Signal
for this probe was split and found on 12q and 15q terminal, suggesting
the presence of t(12;15)(p13;q25), which could not be detected using a
conventional technique (Fig 2). However,
no signal remained on 12p. Further analysis by FISH using cosmid probes
2G8 and 148B69 suggested that the 5
portion of the TEL
gene would be translocated to 15q and the 3 portion to 12q (data not
shown). Then, two novel fusion partners of the TEL gene are expected in
the present case.
View larger version (102K):
[in this window]
[in a new window]
| Fig 2.
The mapping of YAC 964c10 (red) and cosmid D12Z3 (green)
to a leukemia cell. The latter is a centromere probe for chromosome 12. The normal and rearranged chromosome 12 are indicated by an arrowhead
and a large arrow, respectively. der(15) chromosome is identified with
a short arrow. YAC 964c10 hybridized to the normal chromosome 12 and
der(12) as well as to the der(15) chromosome. Signals on the der(12)
are smaller than those on the other chromosomes
|
|
Misao Setoyama
Arinobu Tojo
Fumitaka Nagamura
Shigetaka Asano
Department of
Hematology/Oncology
The Institute of Medical Science
University of
Tokyo
Tokyo, Japan
Minenori Ishimae
Mariko Eguchi
Nanao Kamada
Department of Cancer Cytogenetics
Division of Molecular
Biology
Research Institute for Radiation Biology and
Medicine
Hiroshima University
Hiroshima, Japan
| |
REFERENCES |
1.
Kobayashi H,
Montgomery KT,
Bohlander SK,
Adra CN,
Lim BL,
Kucherlapati RL,
Donis-Keller H,
Holt MS,
Le Beau MM,
Rowley JD:
Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases.
Blood
84:3473,
1994[Abstract/Free Full Text]
2.
Golub TR,
Baker GF,
Lovett M,
Gilliland DG:
Fusion of PDGF receptor b to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.
Cell
77:307,
1994[Medline]
[Order article via Infotrieve]
3.
Papadonpoulos P,
Ridge SA,
Boucher CA,
Stocking C,
Wiedermann LM:
The novel activation of ABL by fusion to est-related gene, TEL.
Cancer Res
55:34,
1995[Abstract/Free Full Text]
4.
Goulb TR,
Barker GF,
Bohlander SK,
Hiebert SW,
Ward DC,
Bray-Ward P,
Morgan E,
Raimondi SC,
Rowley JD,
Gilliland DG:
Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.
Proc Natl Acad Sci USA
92:4917,
1995[Abstract/Free Full Text]
5.
Larripa I,
Mecucci C,
Testoni N,
Bosly A,
Doyen C,
Tytgat H,
van den Berghe H:
Inversion of chromosome 12 in human malignancies.
Cancer Genet Cytogenet
28:113,
1987[Medline]
[Order article via Infotrieve]
6.
Huret JL,
Brizard A,
Briault S,
Dreyfus B,
Giraud C,
Tanzer J:
Two additional cases of inv(12) in human malignancies.
Cancer Genet Cytogenet
32:309,
1988[Medline]
[Order article via Infotrieve]
7.
Hasegawa Y,
Sakai N,
Toyama M,
Ninomiya H,
Abe T:
Chronic myelomonocytic leukemia transformed from refractory anemia with ringed sideroblasts with a rare abnormal chromosome, inv(12).
Jpn J Clin Hematol
31:75,
1990
8.
Huret JL,
Brizard A,
Guilhot F,
Couet D,
Schoenwald M,
Savage JRK,
Tanzer J:
INV(12)(p13q11) and dicentric chromosomes in a secondary leukemia with basophilia.
Hametologica
75:473,
1990
9.
Mathijs B,
Pieter P,
Caiying G,
Jeroen A,
Peter M:
Genomic organization of TEL: The human ETS-variant gene 6.
Genome Res
6:404,
1996[Abstract/Free Full Text]
