0165-4608/98/$19.00
PII S0165-4608(98)00041-7
Cancer Genet Cytogenet 105:198–199 (1998)
Elsevier Science Inc., 1998
655 Avenue of the Americas, New York, NY 10010
LETTER TO THE EDITOR
Severe Hypodiploidy in Refractory Anemia with Excess
Blasts in Transformation
Severe hypodiploidy rarely occurs in cases of leukemia
and may reflect a minimal chromosomal requirement for
cell survival. Although most cases of severe hypodiploidy
are associated with childhood acute lymphoblastic leuke-
mia (ALL), there are rare reported cases in both acute my-
elogenous leukemia and chronic myelogenous leukemia
in blast crisis. However, to our knowledge, severe hypo-
diploidy has not been reported in cases of myelodysplasia.
We report a unique case of a stable, severely hypodiploid
clone in a case of refractory anemia with excess blasts in
transformation (RAEB-t).
An 80-year-old woman presented to her local physician
after an episode of vertigo. In the months previous, her
family noted confusion, disorientation, and incontinence.
Ten years previously, she was diagnosed with poly-
cythemia vera; treatment consisted of phlebotomy and hy-
droxyurea. Hematologic data at the most recent presen-
tation included a normocytic normochromic anemia
(hemoglobin
ϭ
9.3 g/dl, Mean corpuscular volume
ϭ
91fL), thrombocytopenia (platelets
ϭ
69,000/mm
3
), and a
white blood cell count of 1,700/mm
3
with 10% peripheral
blasts. The bone marrow was of increased cellularity with
a myeloid: erythroid ratio of 3:1. Erythropoiesis was left-
shifted with increased proerythroblasts. Granulopoiesis
showed loss of nuclear-cytoplasmic synchrony; the 8%
blasts had scant cytoplasm and one to three prominent nu-
cleoli. A diagnosis of myelodysplastic syndrome/refrac-
tory anemia with excess blasts in transformation was
made. Because of the patient’s age and dementia, she was
not given aggressive therapy and was transferred for hos-
pice care.
Forty cells were analyzed from a 24-hour unstimulated
bone marrow culture. Thirty-one cells appeared normal [46,
XX], whereas nine cells (22%) represented a single hypo-
diploid clone with 35 chromosomes and three structural re-
arrangements: [35,X,
Ϫ
X,
Ϫ
4,
Ϫ
5,
Ϫ
6,
Ϫ
7,
Ϫ
10,
Ϫ
13,
Ϫ
14,
Ϫ
15,
Ϫ
16,
Ϫ
17,
Ϫ
18,del(20)(q13.1),der(22)t(22;?)(p11.2;?),
ϩ
mar].
To further define this clone, cells were stained with
propidium iodide for flow cytometric DNA content analy-
sis using a hypotonic citrate method [1]. A calibrator, cyto-
preserved mononuclear cells from a “normal” donor, was
processed in parallel for the purposes of localizing the
diploid DNA distribution. Data acquisition was performed
on an EPICS(R) Profile II, with list-mode files containing
all events above a discriminator set on the propidium io-
dide signal. List mode files were analyzed “off-line” using
Modfit(R) (Verity Software House, Topsham, ME), a cell-
cycle analysis program. A hypodiploid DNA distribution
(DNA Index
ϭ
0.80), accounting for approximately 20% of
all nuclei examined was identified (Fig. 1), consistent
with the cytogenetic findings.
Severe hypodiploidy has not previously been described
in cases of myelodysplastic syndrome. RAEB-t represents
the most aggressive form of the myelodysplastic syn-
drome; 60% will progress to acute leukemia and the mean
survival is less than six months [2]. Approximately 60% of
patients with RAEB-t have chromosomal aberrations. This,
compared to the one-third to one-half of all patients with
myelodysplastic syndrome having clonal chromosomal
abnormalities, echoes the axiom that the closer myelodys-
plastic syndrome is to overt acute myelogenous leukemia,
the greater the chances of recognizable aberrations. The
progression from polycythemia vera in this case to RAEB-t
is not uncommon. In a 10-year follow-up study of poly-
cythemia vera, 11.4% of patients progressed to acute leu-
kemia or refractory anemia with excess blasts [3].
The most common chromosomal aberrations in RAEB-t
mimic those in other myelodysplastic subgroups: deletion
of the long arm of chromosome 15, monosomy 5 and 7, de-
letion of 7q, and trisomy 8 [4]. While hypodiploidy may
occur, severe hypodiploidy, to our knowledge, has not
been reported previously. Hypodiploidy in clonal popula-
tions of leukemia is most commonly found in childhood
acute lymphoblastic leukemia. The vast majority of these
hypodiploid cases have 45 chromosomes, however. In a
study of 2,184 children with acute lymphoblastic leuke-
mia, only 27 had fewer than 45 chromosomes [5]. Nine-
teen of the 27 had a clonal modal number less than 40,
and most of those had a near-haploid subgroup. Compared
to other ploidy groups (normal, pseudodiploid, and hyper-
diploid), hypodiploidy portends a poorer prognosis. Note-
worthy is a case of ALL in a 55-year-old female who had
both a severely hypodiploid clone and a near-triploid
clone, who died 10 months after diagnosis [6].
Similarly, severe hypodiploidy in acute myelogenous
leukemia confers a poor prognosis. In 15 reported cases,
there is a male predominance and an excess of erythroleu-
kemia; survival in most cases was less than three months
[7]. Interestingly, one case had preceding polycythemia
vera [8]. While the hypodiploid modal number in these