Written in
Featured research from recent issues of Blood
PAPER SPOTLIGHT
EDITOR’S NOTE:
The World Health Organization
also revised its classification of
lymphoid neoplasms, published
in the March 15, 2016, edition
of Blood. Look for our previous
coverage of these revisions in
“What To Call What We Treat,
Part I: WHO Releases Updated
Classification of Lymphoid
Neoplasms” in our May issue.
20
ASH Clinical News
What To Call What We Treat, Part II:
WHO Releases Updated Classification of
Myeloid Neoplasms and Acute Leukemia
Advances in the identification of unique biomarkers associated with
some myeloid neoplasms
and acute leukemias –
thanks in part to geneexpression analyses and
next-generation sequencing – have prompted the
World Health Organization (WHO) to update its
2008 publication on the
classification of tumors
of the hematopoietic and
lymphoid tissues.1
The revised monograph
was recently published in
Blood, along with a revision of the WHO’s 2008
classification of lymphoid
neoplasms.
“This 2016 classification is not a major overhaul
of the disease categories.
Rather, it is intended to
incorporate new knowledge
of these disorders obtained
since the 2008 publication
and is a revision of that
classification,” the authors,
led by Daniel A. Arber, MD,
from Stanford University
in Stanford, California,
explained.
“With respect to
myeloid neoplasms, Dr.
Arber and colleagues emphasize that many novel
molecular findings with
diagnostic and/or prognostic importance have been
incorporated into the 2016
revision,” Mario Cazzola,
MD, an associate editor of
Blood, wrote in an editorial
accompanying the updated
classification.2 “[This revision] represents the efforts
of pathologists working
closely with clinicians and
geneticists. In the next few
years, we should continue
this collaboration to further
improve the integration of
clinical features, morphology, and genetics.”
The revised recommendation is necessary due to
the discoveries in diagnostic
and prognostic markers;
improved characterization
and standardization of morphologic features; and the
clinical-pathologic studies
that call for an integrated
approach incorporating
hematologic, morphologic,
cytogenetic, and molecular
genetic findings.
To develop this
new monograph, the
WHO convened a clinical advisory committee
in early 2014 comprising
nearly 100 pathologists,
hematologists, oncologists, and geneticists to
propose revisions to the
2008 classification.
Read below for some
of the major and proposed
changes. For the full updated classification, visit
bloodjournal.org.
Myeloproliferative
Neoplasms
The categories of myeloproliferative neoplasms
(MPNs) have not significantly changed since the
2008 edition, the authors
noted, “but discoveries of
new mutations and improved understanding of
the morphologic features
of some entities have
impacted the diagnostic
criteria for the disease
entities.”
Chronic myel oid leukemia (CML), BCR-ABL1–
positive: Most cases of CML
can be diagnosed from
peripheral blood findings
combined with detection
of t(9;22)(q34.1;q11.2) or
BCR-ABL1. Newly diagnosed patients have a
much better prognosis
when treated with tyrosine
kinase inhibitors (TKIs),
but regular monitoring for
BCR-ABL1 and the potential
for TKI resistance should
be conducted to detect
disease progression.
»»Smoldering systemic
the authors explained.
MDS/MPN with ring
sideroblasts and thrombocytosis has been converted
from a provisional to a full
entity.
Chronic myelomonocytic leukemia (CMML):
Targeted sequencing of
mutated genes can detect
a high proportion of cases,
with SRSF2, TET2, and
ASXLI being the most
commonly mutated genes.
Newly diagnosed CMML
requires both the presence
of persistent monocytosis
≥1 x 109/L and monocytes
accounting for ≥10 percent
of the white blood cell
differential count. CMML
is now separated into two
subtypes: proliferative type
(white blood cell [WBC]
count ≥13x109/L) and
dysplastic type (WBC count
<13 x 109/L) with differences related to aberrancies in
the RAK/MAPK signaling
pathways.
»»Systemic mastocyto-
Myelodysplastic
Syndromes
Mastocytosis
Mastocytosis: Discoveries
of new genetic mutations
associated with these
diseases have changed
their diagnostic criteria.
Mastocytosis is no longer
considered a subgroup
of the MPNs due to its
unique clinical and pathologic features and is now a
separate disease category
in the classification. Under
its own classification,
mastocytosis includes:
• Cutaneous mastocytosis
• Systemic mastocytosis
»»Indolent systemic
mastocytosis
mastocytosis
sis with an associated hematologic
neoplasm
»»Aggressive systemic
mastocytosis
»»Mast cell leukemia
• Mast cell sarcoma
Myelodysplastic/
Myeloproliferative
Neoplasms
The myelodysplastic
syndromes (MDS)/MPN
category was introduced
in the third edition of the
WHO classification to include MPNs with clinical,
laboratory, and morphologic features that overlap
between MDS and MPN,
The updated guidelines
have changed the terminology for adult MDS
to remove “refractory
anemia” and “refractory
cytopenia” and replaced
them with MDS with
the following modifiers:
single versus multi-lineage
dysplasia, ring sideroblasts,
excess blasts, or the del(5q)
cytogenetic abnormality.
No changes were made for
childhood MDS.
Since the 2008 monograph, a large amount
of data are available on
recurring mutations in MDS.
Targeting sequencing can
detect mutations in 80 to
90 percent of MDS patients,
the most common of which
are SF3B1, TET2, SRSF2,
ASXL1, DNMT3A, RUNX1,
U2AF1, TP53, and EZH2. The
TP53 mutation is associated
with aggressive disease in
MDS and appears to predict
poorer response to lenalidomide treatment in patients
with del(5q).
This monograph
includes a section on
myeloid neoplasms with
germline predisposition,
including the following:
• Myeloid neoplasms
with germline predisposition without a
preexisting disorder or
organ dysfunction
• Myeloid neoplasms
with germline predisposition and preexisting
platelet disorders
• Myeloid neoplasm with
germline predisposition and other organ
dysfunction
Acute Myeloid
Leukemia
A new provisional category
of acute myeloid leukemia (AML) with BCR-ABL1
has been established to
recognize these rare, de
novo AML cases that may
benefit from treatment
with TKI therapy. Though
the diagnostic distinction
between de novo AML
with BCR-ABL1 and blast
transformation of CML
may be difficult to distinguish, the significance
of detecting this targetable fusion is important.
Preliminary data suggest
that deletion of antigen
receptor genes (IGH, TCR),
IKZF1, and CDKN2A may
support a diagnosis of de
novo AML with BCR-ABL1
versus BP-CML.
AML with CEBPA is
June 2016