Acute Leukemias - Republican Scientific Medical Library

a 8.5 · Cytogenetic and Molecular Abnormalities 123
8.4.6 Natural Killer ALL (Blastic NK)
Rare cases of ALL have been reported in which the
blasts lack myeloid and lymphoid markers (CD3 and
CD19) but express CD56. These cases are classified as
ALL of the natural killer cell phenotype. Blastic NK cells
may show cytoplasmic CD3 and, occasionally, other Tcell
markers (CD4 or CD7), and can be positive or negative
for TdT. They lack evidence of T-cell receptor gene
rearrangement. These cases should be distinguished
from myeloid leukemia that expresses myeloid markers
in addition to CD56. Expression of CD56 can also be
seen in some cases that are typically lymphoblastic,
with clear T-cell surface markers. Such cases should
be considered precursor T-cell ALL with CD56 expression
[52, 61, 71].
8.4.7 Biphenotypic and Bilineage ALL
In biphenotypic leukemia, markers specific for lymphoid
as well as myeloid lineages can coexist in the
same blast population. When two distinct cell populations
coexist, one with lymphoid and the other with
myeloid markers, the term “bilineage” applies. Biphenotypic
and bilineage ALL are lumped together with other
undifferentiated subtypes in the WHO classification of
“acute leukemia of ambiguous lineage.” Despite significant
confusion over the terminology, there is agreement
that cells of ALL can express CD13 or CD33 or both,
especially when they are positive for Philadelphia chromosome.
These cases should be called “ALL with myeloid
markers” rather than “biphenotypic ALL.”
Biphenotypic ALL is characterized by the expression
of lymphoid markers (CD19 with TdT or CD3 with
TdT) along with myeloid markers (MPO with CD13, or
MPO with CD33). Several scoring systems can be used
for the diagnosis of biphenotypic ALL; the Immunologic
Classification of Leukemia is the most widely accepted
[4, 75]. The importance of classification is to decide
whether a patient should be treated for lymphoblastic
leukemia or for myeloid leukemia. For practical
purposes, MD Anderson Cancer Center uses a simplified
approach for classifying these cases with ambiguous
lineage or minimal differentiation. This approach
is based on blasts being negative for MPO and NSE
and positive for TdT (Fig. 8.3). If these blasts express
one of the major lymphoid markers (CD10, CD19,
CD3) or two of the other lymphoid markers, the case
Fig. 8.3. Schematic approach for a clinically useful diagnosis of
leukemia of ambiguous lineage (minimally differentiated) as used by
MD Anderson Cancer Center.
is classified as lymphoblastic leukemia, irrespective of
whether myeloid markers are expressed [4, 14, 31, 49,
71]. Patients who have one myeloid marker but fewer
than two lymphoid markers (other than CD19, CD3, or
CD10) are classified as having ALL with minimal differentiation.
8.4.8 MPO-Positive ALL
This term should be reserved for rare cases of ALL that
demonstrate typical lymphoid markers without myeloid
markers, except for strong positivity (20–30%) for MPO.
Most of these cases show lymphoblasts with deep basophilic
cytoplasm [82]. These cases should be distinguished
from Burkitt cases as well as AML.
8.5 Cytogenetic and Molecular Abnormalities
Approximately 45% of ALL cases demonstrate recurrent
ALL-specific cytogenetic abnormalities on conventional
karyotyping studies, establishing cytogenetic study as a
valuable diagnostic and prognostic tool for evaluating
patients with ALL. In addition, most of these abnormalities
can be detected using fluorescence in-situ hybridization
(FISH), Southern blotting of genomic DNA, and
reverse transcription-polymerase chain reaction (RT-
PCR) of mRNA. FISH and RT-PCR are used to detect
minimal residual disease and to monitor patients after
therapy; real-time RT-PCR allows the quantitative monitoring
of residual disease. The most common cytogenetic
abnormalities are listed in Table 8.1 and discussed
below.