Leugemta Research V o l 9. No. 12, p p 1467-1473. 1985. 0145-2126/8553.00 -~ .

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Printed m Greal Britain Lt, 1985 Pergamon Press L i d

11;19 TRANSLOCATION IN A CONGENITAL

LEUKEMIA WITH TWO CELL POPULATIONS OF
LYMPHOBLASTS AND MONOBLASTS

YASUHIDE HAYASHI*, MASAHARU SAKURAI,~YASUHIKOKANEKO,t TAKASHIABE,:~

TAIJIRO MORI:~and SHINPEI NAKAZAWA++
*Division of Hematology/Oncology, Saitama Children's Medical Center,
tHematology Clinic, Saitama Cancer Center and
:~Department of Pediatrics, Kelp University Hospital, Japan

(Received 28 February 1985. Revision accepted 12 June 1985)

Abstract--This report describes a case of a female infant of congenital leukemia with a

chromosomal translocation t(l 1;19) (q23;p13) which presented initially with lymphoid features
and at relapse with monocytic ones. The clinical course and the results of sequential cytochemical,
cytogenetic and immunological studies are considered to be consistent with the interpretation of
leukemogenesis of the myelo-monocytoid progenitor cell which still retains the capability of ex-
hibiting lymphoid features to a limited extent. Although leukemia with t(l 1;19) has been classified
as ANLL, most commonly M5 of FAB classification, the patient with this chromosomal abhor.
mality may have a mixed leukemia in which cells with lymphoid features and those with monocytic
ones exist.

Key words: ALL, AMOL, mixed leukemia, congenitial leukemia, chromosome abnormality,
t(11;19).

INTRODUCTION CASE REPORT

THE POSSIBLEexistence of a common lymphoid-myeloid
stem cell in humans has continued to be a subject of
controversy. Several cases with mixed lymphocytic and
non-lymphocytic leukemia have so far been reported [2,
7, 9, 13, 16]. Most such cases have been revealed to be
biphenotypic by cytochemical staining and immuno-
logical techniques, and to have normal karyo-
types. Recent ultrastructural and immunological studies
of acute leukemias with the t(4;ll) chromosome rear-
rangement have indicated that the lymphoid-appearing
blast possess features suggesting myeloid origin [10,12].
This report describes an infant of congenital leukemia
with t(ll;19) who presented with leukemic cells with
lymphoid features initially and with monocytic ones at
relapse.
Abbreviations." ANLL, acute nonlymphocytic leukemia;
ALL, acute lymphocytic leukemia; CML, chronic myelo-
genous leukemia; PAS, periodic acid-Shift; a-NBE, a-naphtyl
butyrate esterase; E, spontaneous rosette formation with sheep
erythrocytes; EA, receptor for Fe portion of lgG; EAC, recep-
tor for complement; la, human la-like antigens; CALLA, com-
mon ALL antigen; Slg, cell surface immunoglobulin.
Correspondence to: Dr Yasuhide Hayashi, Division of
Hematology/Oncology, Saitama Children's Medical Center
2100 Magome, lwatsuki, Saitama 339, Japan.
This female infant was born on December 31, 1982, to
healthy parents after 38 weeks' gestation and weighed
2.88kg. On the fourth day of birth she was admitted to
the National Tochigi Hospital with anemia, skin erup-
tion with nodules and hepatosplenomegaly. On admis-
sion her hemoglobin was 7.3g/dl, platelet count 5.6 x
109/1 and white blood cells (WBC) 2.59 x I06/1 with
94.5070 blasts (Fig. la) which were small to medium in
size and were positive for PAS staining and negative for
peroxidase, t~-NBE and acid phosphatase. Cell surface
marker studies using rosette formation, heteroantiserum
and monoclonal antibodies revealed these cells to be
E(-), EA(-), SIg(-), KOR-Ia17 (Ia)(+)(95.0070), KOR-
N34 (CALLA)( + )(68.1%) [11] and MCS- 2( + )(45.7070)
[5]. TdT activcity was negative. The serum lysozyme
value was 16.2pg/ml. She was diagnosed as having acute
lymphocytic leukemia (ALL, L2 of FAB classification),
and was treated with vincristine (VCR) and prednisolone
(PSL) and obtained complete remission (CR) on
January 25, 1983. Her WBC, however, gradually in-
creased and reached 245.6 x 109/1 with 92.507o blasts
on March 8. At this time the blasts (Fig. lb) were
medium to large in size with abundant cytoplasm and a
lobulated nucleus. They ingested Latex particles, and
were positive for peroxidase and a-NBE staining. The
serum lysozyme value was as high as 1140~g/ml. Cell
surface marker studies using the same above methods
were performed on these cells, but resulted in
unevaluable estimation because of non-specific reaction
of the antibodies with the IgG-Fc receptors. These

1467
1468 YASUHIDEHAYASHIet al.

0 . 2. . 4. . ~ 0 iO 12 . 1.4 . a.6 . .~ . ~ . z.2

weeks
VCRv v v v v v vv v vv v v v

6MP ql I -~
MTX a o . o o a
BHAC
ADM ~

jyS(~Zl)~I6.2 23.4 1114.0 36.3 90,6 14.1 373 juq/mi

skin mamrnory glond
Infi,rmim ~ --

FIG.2. Clinical course of the patient. BH-AC : enocitabine;

MTX : methotrexate; ADM : adriamycin.

features of the leukemic cells were compatible with those DISCUSSION

of acute monocytic leukemia (AMOL, M5b of FAB
classification). She was treated with VCR, methotrex-
ate, 6-mercaptopurine (6-MP) and PSL without obtain-
ing remission. At this time the blast consisted of two
populations of small immature lymphoblasts and ap-
parently mature monoblasts. She was given two courses
of combination chemotherapy with adriamycin,
enocitabine, 6MP, VCR and PSL, and obtained CR
(Fig. 2). She had been in CR for 7 months before she
relapsed and died.
CYTOGENETIC STUDIES
Peripheral blood samples were obtained at diagnosis
in January, 1982 prior to treatment and at the first
relapse in March, 1982. They were cultured for 24,48
and 72 h without pbytohemagglutinin (PHA) and 72 h
with PHA. Sixteen metaphases were analysed with
Giemsa (G) [15] or quinacrine (Q) [3] banding methods
prior to treatment. Thirteen cells were found to have
46,XX,t(ll;19) (q23;pl3) (Fig.3.) and the other 3 a
normal female karyotype (46,XX). At first relapse,
twenty three metaphases were analyzed with G- or
Q-banding methods, of which 16 cells showed 46,XX,
t(ll;19) (q23;p13), 3 showed 47,XX,+6, t(ll;19)
(q23;pl3) and 4 showed 47,XX, + 8, -1 l, -19, +der (1 l)
t(ll;19) (q23;p13), +i(19p+). The i(19p+) could also
be designated as der( 19)t( 11 ; 19)(I Iqter ~ l 1q23 :: 19p 13
• 19cen::19cen ~19p13::llq23 -,llqter)(Fig. 4).
The results of the morphological, cytochemical and
immunological studies in our patient strongly suggest
that the newborn girl had a congenital mixed leukemia.
Her leukemic cells initially showed lymphoid features
and later monocytic ones. The cause of this pheno-
menon is unknown. One possibiltiy is that the disease
originated with two concomitant malignant trans-
formations in both lymphoid and monocytoid precursor
cells. This might, of course, be a very unusual clinical
event. A more likely possibility might be that malignant
transformation at the pluripotential stem cell level was
followed by differentiation into the two cell lineages,
lymphoid and monocytoid. The fact that the two types
of blasts had a common chromosone abnormality,
t(l 1; 19), suggests that they were derived from a common
stem cell.
Immunological studies in our case revealed that
reaction to monoclonal antibody MCS-2, which reacts
to cells in the myeloid lineage [5], was positive both at
the times of diagnosis and relapse. This finding suggests
the possibility that the myeloid progenitor cell may at
some stage of differentiation have had morphological
and biochemical features that are commonly attributed
to lymphoid cells rather than the possibility that the
proliferation process involved the bone marrow
precursor cell that had the capability to differentiate
towards both myeloid and lymphoid cells.
Blastic crisis of CML and acute leukemia with Ph ~
 '!
J

!
m, k

FIG. la: Peripheral blood smear at initial diagnosis, showing

small lymphoblasts with coarse nuclear chromatin and scanty
cytoplasm and no granulation. May-Giemsa stain ( x 1000).
(b): Peripheral blood smear at relapse, showing large
monoblasts with lobulated nucleus with fine chromatin pattern
and abundant cytoplasm. May-Giemsa stain ( × 1000).

1469
FIB.3. Karyotype of a leukemic cell at diabnosis, showing
46,XX, t(ll;19)(q23;p13).

1470
 /

11 llq- 19

FIc.4. Partial karyotype of a leukemic cell at relapse. The ar-

row shows i(19p + ).

1471
 Mixed congenital leukemia with t(11;19)
c h r o m o s o m e have been r e p o r t e d to show various cell
m o r p h o l o g i e s or m e m b r a n e p h e n o t y p e s . Even t h o u g h
several mixed leukemia cases have been reported so far
[2, 7, 9, 13, 16], cytogentic studies, which were per-
f o r m e d on some of t h e m , only r e p o r t e d n o r m a l karyo-
types [2, 16]. Recently cells of acute leukemia with a
t ( 4 : l l ) , which generally show l y m p h o i d a p p e a r a n c e ,
were s h o w n to possess features o f myeloid precussor cell
characteristics by u l t r a s t r u c t u r a l a n d i m m u n o l o g i c a l
studies. [12].
T h e k a r y o t y p e o f o u r patient were s h o w n to be 46,X-
X, t(11;19) (q23;p13) at diagnosis, a n d additional ab-
n o r m a l i t i e s of + 6 or + 8 a n d i ( 1 9 p + ) a p p e a r e d at
relapse. Even t h o u g h the 11q23 i n v o l v e m e n t is com-
m o n l y observed in A M O L [1, 4, 6, 8], cells o f some
cases with 11q23 a b n o r m a l i t i e s such as t ( 4 ; l l ) and
t(11 ; 19) m a y be of early m y e l o - m o n o c y t o i d p r o g e n i t o r
origin capable of exhibiting l y m p h o i d features to a
limited extent.
Rovigatti et al. recently reported t h a t heavy chain im-
m u n o g l o b u l i n gene r e a r r a n g e m e n t was f o u n d in A N L L
in children [14]. It is possible t h a t mixed leukemia with
the 11q23 a b n o r m a l i t y may be a candiate t h a t has such
rearrangements.
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