Recent changes in 2016 who classification of myeloid neoplasm
1. Recent Changes Made In 2016
WHO Classification Of Myeloid
Neoplasms
Presenter: DR. POOJA DWIVEDI (JR1)
Moderator: DR. NISHANT TAUR
DEPARTMENT OF PATHOLOGY, K.G.M.U.
2. Society for Haematopathology
the European Association
for Haematopathology
the World Health
Organization (WHO)
third and fourth editions of the WHO
Classification of Tumours of Haematopoietic
and Lymphoid Tissues, in 2001 and 2008,
respectively, as part of a series of WHO
Classification of Tumours “Blue book”
monographs
3. The purpose of this presentation is to summarize the major
changes in the revised WHO classification of myeloid
neoplasm and acute leukaemia and to provide the rationale
for those changes
The revision of fourth edition follows the philosophy of third
and fourth edition to incorporate clinical features,
morphology, immunophenotyping, cytogenetics and
molecular genetics to define disease entities of clinical
significance
4. • This revision has been influenced by several factors including
the following:
1. The discovery of recently identified molecular features has
yielded new perspectives regarding diagnostic and
prognostic markers that provide novel insights for the
understanding of the pathobiology of these disorders
2. Improved characterization and standardization of
morphological features aiding in the differentiation of
disease groups, particularly of the BCR-ABL1-
myeloproliferative neoplasms (MPNs), has increased the
reliability and reproducibility of diagnoses
3. A number of clinical-pathological studies have now validated
the WHO postulate of an integrated approach that includes
hematologic, morphologic, cytogenetic, and molecular
genetic findings
5. Myeloproliferative Neoplasm
• The categories of MPNs have not significantly changed since
the 2008 fourth edition of the classification
• Discoveries of new mutations and improved understanding of
the morphologic features of some entities have impacted the
diagnostic criteria for the disease entities
• Mastocytosis is no longer a subgroup of the MPNs due to its
unique clinical and pathologic features, ranging from indolent
cutaneous disease to aggressive systemic disease and is now a
separate disease category in the classification
6.
7. Chronic Myeloid Leukaemia
• Most cases of CML(BCR-ABL1+) in chronic phase can be
diagnosed from peripheral blood findings combined with
detection of t(9;22)(q34.1;q11.2)
• More specifically,BCR-ABL1 by molecular genetic techniques
• Still bone marrow(BM)aspirate is essential to ensure sufficient
material for a complete karyotype and for morphologic
evaluation to confirm the phase of disease
• The accelerated phase (AP) of CML is becoming less common
in the era of TKI therapy and still there are no universally
accepted criteria for its definition
8. • A “Provisional” criteria for AP included depending on
hematologic, morphologic, and cytogenetic parameters which
are supplemented by additional parameters attributed to
genetic evolution and manifested by evidence of resistance
to TKIs
• Diagnosis of blast phase (BP) still requires either at least 20%
blasts in the blood or BM or extramedullary accumulation of
blasts
• As the onset of lymphoid BP may be quite sudden, the
detection of any bona fide lymphoblasts in the blood or
marrow should raise concern for a possible impending
lymphoid BP, and prompt additional laboratory and genetic
studies to exclude this possibility
12. 2016 CNL
• The CSF3R mutation is
strongly associated
with chronic
neutrophilic leukaemia
(CNL)
• Approx 90% CNL cases
have CSF3R mutation
13. POLYCYTHAEMIA VERA
• Polycythaemia Vera (PV) is possibly underdiagnosed using the
haemoglobin levels published in the fourth edition, and the
utility of BM morphology as a reproducible criterion for the
diagnosis of PV is recognized
• So required haemoglobin levels as a criteria are reduced and
incorporated with PV bone marrow morphology to prevent
underdiagnoses of PV
14.
15. PRIMARY MYELOFIBROSIS
• Primary myelofibrosis (PMF) is a myeloproliferative neoplasm
(MPN) characterized by stem cell‐derived clonal
myeloproliferation that is often but not always accompanied
by JAK2, CALR or MPL mutation and bone marrow fibrosis
• According to 2016 WHO classification PMF is divided into
“pre-fibrotic” PMF (pre‐PMF) and “overt fibrotic” PMF, The
pre-PMF might mimic ET in its presentation and it is
prognostically relevant to distinguish the two
• The presence of JAK2, CALR or MPL mutation is supportive but
not essential for diagnosis
• Approximately 90% of patients carry one of these mutations
and 10% are “triple‐negative”
16.
17.
18. ESSENTIAL THROMBOCYTOSIS
• Essential thrombocythaemia (ET) is a chronic
myeloproliferative neoplasm that primarily involves the
megakaryocytic lineage
• It is characterized by sustained thrombocytosis and increased
numbers of large, mature megakaryocytes in the bone
marrow
• Clinically characterized by occurrence of thrombosis and/or
haemorrhage
• Because there is no known genetic or biological marker
specific for ET, other causes of thrombocytosis must be
excluded
19.
20.
21. CHRONIC EOSINOPHILIC LEUKAMIA ,NOS
• It is an autonomous, clonal proliferation of eosinophil
precursors results in persistently increased numbers of
eosinophils in the peripheral blood, bone marrow, and
peripheral tissues, with eosinophilia being the dominant
haematological abnormality
23. MYELOPROLIFERATIVE NEOPLASM, UNCLASSIFIABLE
• Myeloproliferative disease, unclassifiable (CMPD, U) should
be applied only to cases that have definite clinical, laboratory
and morphologic features of a myeloproliferative disease, but
that fail to meet the criteria for any specific MPD entities or
• Present with features that overlap two or more of MPN
categories
24. Most cases of MPN-U fall into one of three groups:
1. A subset of cases with so-called masked pre- polycythaemia
presentation of PV, early primary myelofibrosis, or Early-
phase essential thrombocythaemia in which the
characteristic features are not yet developed and that fail to
meet the diagnostic criteria for any of the specific MPN
entities may also be considered to belong in this group
2. Advanced-stage MPN, in which pronounced myelofibrosis,
osteosclerosis, or transformation to a more aggressive stage
with increased blast counts and/or myelodysplastic changes
obscures the underlying disorder
3. Cases with convincing evidence of an MPN in which a
coexisting neoplastic or inflammatory disorder obscures
some of the usual diagnostic clinical and/or morphological
features
25. • Exclusionary criteria :
The presence of BCR-ABL 1 fusion; rearrangement of
PDGFRA, POGFRB, or FGFR1; or PCM1-JAK2 fusion excludes the
diagnosis of MPN-U
26.
27. MASTOCYTOSIS
• No longer considered a subgroup of the MPNs due to its
unique clinical and pathologic features, ranging from indolent
cutaneous disease to aggressive systemic disease
• Mastocytosis is now a separate disease category in
classification
• Also there is shortening of the name of the 2008 category of
“systemic mastocytosis with associated clonal haematological
non-mast-cell lineage disease (SH-AHNMD)” to the 2016
category of “systemic mastocytosis with an associated
haematological neoplasm (SM-AHN)”
29. Diagnostic criteria for cutaneous and systemic
Mastocytosis
Cutaneous mastocytosis
• Skin lesions demonstrating the typical findings of urticaria
pigmentosa/maculopapular cutaneous mastocytosis, diffuse
cutaneous mastocytosis or solitary mastocytoma, and typical
histological infiltrates of mast cells in a multifocal or diffuse
pattern in an adequate skin biopsy
• In addition, features/criteria sufficient to establish the
diagnosis of systemic mastocytosis must be absent. There are
three variants of cutaneous mastocytosis
30. Systemic mastocytosis
• The diagnosis of systemic mastocytosis can be made when the
major criterion and at least 1 minor criterion are present, or
when 2 3 minor criteria are present
Major criterion –
Multifocal dense infiltrates of mast cells (215 mast cells in
aggregates) detected in sections of bone marrow and/or other
extracutaneous organ(s)
31. Minor criteria-
1. In biopsy sections of bone marrow or other extracutaneous
organs, > 25% of the mast cells in the infiltrate are spindle-
shaped or have atypical morphology or > 25% of all mast
cells in bone marrow aspirate smears are immature or
atypical
2. Detection of an activating point mutation at codon 816 of
KIT in the bone marrow, blood or another extracutaneous
organ
3. Mast cells in bone marrow, blood or another extracutaneous
organ express CD25, with or without CD2, in addition to
normal mast cell markers
4. Serum total tryptase is persistently> 20 ng/ml, unless there
is an associated myeloid neoplasm, in which case this
parameter is not valid
32. Diagnostic criteria for the variants of
systemic mastocytosis
A. Indolent systemic mastocytosis
Meets the general criteria for systemic mastocytosis
No C findings
No evidence of an associated haematological neoplasm
Low mast cell burden
Skin lesions are almost invariably present
33. B. Bone marrow mastocytosis
As above (indolent systemic mastocytosis), but with bone
marrow involvement and no skin lesions
C. Smouldering systemic mastocytosis
Meets the general criteria for systemic mastocytosis ≥2 B
findings; no C findings
No evidence of an associated haematological neoplasm
High mast cell burden
Does not meet the criteria for mast cell leukaemia
34. D. Systemic mastocytosis with an associated haematological
neoplasm
Meets the general criteria for systemic mastocytosis
Meets the criteria for an associated haematological neoplasm
(i.e. a myelodysplastic syndrome, myeloproliferative
neoplasm, acute myeloid leukaemia, lymphoma or another
haematological neoplasm classified as a distinct entity in the
WHO classification)
35. E. Aggressive systemic mastocytosis
Meets the general criteria for systemic mastocytosis
≥1 C finding
Does not meet the criteria for mast cell leukaemia
Skin lesions are usually absent
36. F. Mast cell leukaemia
Meets the general criteria for systemic mastocytosis
Bone marrow biopsy shows diffuse infiltration (usually dense)
by atypical, immature mast cells
Bone marrow aspirate smears show ≥20% mast cells
In classic cases, mast cells account for ≥10% of the peripheral
blood white blood cells, but the aleukaemic variant (in which
mast cells account for < 10%) is more common
Skin lesions are usually absent
37. B ('burden of disease') and C ('cytoreduction-requiring') findings in systemic
mastocytosis, which indicate organ involvement without and with organ
dysfunction, respectively
B findings
1. High mast cell burden (shown on bone marrow biopsy): >
30% infiltration of cellularity by mast cells (focal, dense
aggregates) and serum total tryptase > 200 ng/mL
2. Signs of dysplasia or myeloproliferation in non-mast cell
lineage(s), but criteria are not met for definitive diagnosis
of an associated haematological neoplasm, with normal or
only slightly abnormal blood counts
3. Hepatomegaly without impairment of liver function,
palpable splenomegaly without hypersplenism and/or
lymphadenopathy on palpation or imaging
38. C findings
1. Bone marrow dysfunction caused by neoplastic mast cell
infiltration, manifested by ≥1 cytopenia: absolute neutrophil
count < 1.0 x 109 /L, haemoglobin level < 10 g/dL, and/or
platelet count< 100 x 109 /L
2. Palpable hepatomegaly with impairment of liver function,
ascites and/or portal hypertension
3. Skeletal involvement, with large osteolytic lesions with or
without pathological fractures (pathological fractures caused
by osteoporosis do not qualify as a C finding)
4. Palpable splenomegaly with hypersplenism
5. Malabsorption with weight loss due to gastrointestinal mast
cell infiltrates
39. Myeloid/lymphoid neoplasms with
eosinophilia and gene rearrangement
• Myeloid/lymphoid neoplasms with PDGFRA rearrangement
• Myeloid/lymphoid neoplasms with PDGFRB rearrangement
• Myeloid/lymphoid neoplasms with FGFR1 rearrangement
• Myeloid/lymphoid neoplasms with PCM1-JAK2
40.
41. Myeloid/Lymphoid neoplasms with PCM1-JAK2
• New entity-> PCM1-JAK2: t(8;9)(p22;p24.1)
• It is a rare entity which presents with eosinophilia with BM
finding of left sided erythroid predominance, lymphoid
aggregates and often myelofibrosis
• Other Tk rearrangements can also present as B-cell ALL
• Also known as BCR-ABL1 like ALL with t(9;12)(p24;p13)
ETV6/JAK2
• New provisional category for B-cell leukaemia/lymphoma
• Responds to JAK2 inhibition/ TKI
42. Myelodysplastic/myeloproliferative
neoplasms
• The myelodysplastic syndrome (MDS/MPN) category was
introduced in the third edition to include myeloid neoplasms
with clinical, laboratory, and morphologic features that
overlap between MDS and MPN
• Based on accumulated scientific evidence, a provisional entity
within the MDS/MPN unclassifiable group, refractory anaemia
with ring sideroblasts associated with marked thrombocytosis
(RARS-T), has been accepted as a full entity
• It is now termed as MDS/MPN with ring sideroblasts and
thrombocytosis
44. Chronic myelomonocytic leukemia
• Chronic myelomonocytic leukaemia(CMML) is a clonal
haematopoietic malignancy with features of both a
myeloproliferative neoplasm (MPN) and a myelodysplastic
syndrome (MDS)
• In 2016 WHO classification On the basis of the percentage of
blasts and promonocytes in the blood and bone marrow,
CMML cases have been further divided into three
subcategories: CMML-0, CMML-1 and CMML-2
45.
46. 2016
• CMML-0: < 2% blasts in the
blood and < 5% in the bone
marrow; no Auer rods
• CMML-1: 2-4 % blasts in the
blood or5-9% in the bone
marrow; < 5% blasts in the
blood, < 10% blasts in the
bone marrow, and no Auer
rods
• CMML-2: 5-19% blasts in the
blood, 10- 19% in the bone
marrow or Auer rods are
present; < 20% blasts in the
bone marrow and blood
2008
• CMML-1: < 5% blasts in the
blood, < 10% blasts in the
bone marrow, and no Auer
rods
• CMML-2: 5-19% blasts in the
blood, 10- 19% in the bone
marrow or Auer rods are
present; < 20% blasts in the
bone marrow and blood
47. New data in CMML:
• Mutations of SRSF2, TET2, and ASXL1
• One of the three above mutations can be identified in at least
90% of CMML cases; other mutations seen less frequently are
SETBP1, RAS, RUNX1, CBL, and EZH2. They can be helpful
diagnostic adjuncts in difficult cases, particularly given the
frequently normal karyotype of CMML
• Co‐mutation of TET2 and SRSF2 is seen in about one‐third of
CMML cases and is a specific predictor of the diagnosis
• ASXL1 is a predictor of aggressive disease behaviour and has
been incorporated into a prognostic scoring system alongside
karyotype and clinicopathological parameters
• NPM1 mutation is seen in a rare subset of CMML (3‐5%) and
appears to herald a worst prognosis
48. Atypical CML, BCR-ABL 1-NEGATIVE
• The rare MDS/MPN subtype atypical CML (aCML) is now
better characterized molecularly and can be more easily
separated from CNL, a rare subtype of MPN similarly
characterized by neutrophilia
• Although CNL is strongly associated with the presence of
CSF3R mutations, these appear to be very rare in aCML (10%)
• Conversely, aCML is associated with SETBP1 and/or ETNK1
mutations in up to a third of cases
• The so-called MPN-associated driver mutations (JAK2, CALR,
MPL) are typically absent in aCML
49.
50. Juvenile myelomonocytic leukaemia
• Juvenile myelomonocytic leukaemia (JMML) is an aggressive
clonal hematopoietic disorder of infancy and early childhood
characterized by an excessive proliferation of cells of
monocytic and granulocytic lineages
• The clinical and pathological findings of JMML are not
substantially changed from the current WHO fourth edition
(2008)However, molecular diagnostic parameters have been
refined
• Approximately 90%of patients carry either somatic or
germline mutations of PTPN11, KRAS, NRAS, CBL, or NF1
53. Myelodysplastic/myeloproliferative neoplasm with
ring sideroblasts and thrombocytosis
• In the original 4th edition of the WHO classification, refractory
anaemia with ring sideroblasts associated with marked
thrombocytosis (RARS-T) was proposed as a provisional entity
• In 2016 WHO classification MDS/MPN-RS-T has become a
well-characterized, distinct entity
• Particularly following the discovery of a strong association
with SF381 mutations, which are often concurrent with the
JAK2 V617F mutation and less commonly with MPL or CALR
mutation
54.
55. Myelodysplastic / myeloproliferative
neoplasm, unclassifiable
• MDS/MPN-U meets the criteria for the MDS/MPN category in
that at the time of initial presentation, it has clinical,
laboratory and morphological features that overlap with both
myelodysplastic syndrome (MOS) and myeloproliferative
neoplasm (MPN) categories
• The removal of MOS/MPN-RS-T from the category of
MOS/MPN-U is a change from the original 4th edition of the
WHO classification
56. Myelodysplastic Syndrome
• The MDS are a group of clonal BM neoplasms characterized
by ineffective hematopoiesis, manifested by morphologic
dysplasia in hematopoietic cells and by peripheral
cytopenia(s)
• Cytopenia is a “sine qua non” for any MDS diagnosis and in
prior classifications, MDS nomenclature included references
to “cytopenia” or to specific types of cytopenia eg, “refractory
anaemia”
• However, the WHO classification relies mainly on the degree
of dysplasia and blast percentages for disease classification
and specific cytopenia have only minor impact on MDS
classification
57. • Moreover, the lineage(s) manifesting significant morphologic
dysplasia frequently do not correlate with the specific
cytopenia(s) in individual MDS cases
• For these reasons, the Adult MDS has changed to remove
terms such as “refractory anaemia” or cytopenia” and
replaces them with “myelodysplastic syndrome” followed by
the appropriate modifiers: single Vs multilineage dysplasia,
ring sideroblasts etc
• There are no changes to childhood MDS; refractory cytopenia
of childhood remains as a provisional entity within this
category
58. • There is a major change in the diagnostic criteria for myeloid
neoplasms with erythroid predominance erythroid precursors
>50%of all BM cells)
• In the updated classification, the denominator used for
calculating blast percentage in all myeloid neoplasms is all
nucleated BM cells, not just the “non erythroid cells”
• This will result in most cases previously diagnosed as the
erythroid/myeloid subtype of acute erythroid leukemia now
being classified as MDS with excess blast
59.
60. Myeloid neoplasms with germ line
predisposition
• A major change to the 2016 revision of the WHO classification
is the addition of a section on myeloid neoplasms with germ
line predisposition
• It has become increasingly apparent that some cases of
myeloid neoplasms, in particular MDS and AML, occur in
association with inherited or de novo germline mutations
characterized by specific genetic and clinical findings
• These disorders occur in the setting of well-defined inherited
syndromes that exhibit additional non-haematological
findings and often present in childhood, such as the bone
marrow failure syndromes (including Fanconi anaemia) and
the telomere biology disorders (e.g. Dyskeratosis congenita)
65. AML with recurrent genetic
abnormalities
• The WHO continues to define specific acute myeloid leukemia
(AML) disease entities by focusing on significant cytogenetic
and molecular genetic subgroups
• A large number of recurring, balanced cytogenetic
abnormalities are recognized in AML, and most of those that
are not formally recognized by the classification are rare
• In order to stress the significance of PML RARA fusion from
other complex rearrangements other than t(15;17), it is
renamed as APL with PML-RARA
66. • A new provisional category AML with BCR-ABL1 added to
recognize these rare de novo AML cases that may benefit
from TKI therapy
• The finding that the improved prognosis associated with AML
with mutated CEBPA is associated with biallelic, but not single,
mutations of the gene has resulted in a change in that disease
definition to require biallelic mutations
• A provisional category of AML with mutated RUNX1 has been
added to the classification for cases of de novo AML with this
mutation which has possibly worse prognosis than other AML
types
• AML with mutated NPM1 and AML with biallelic mutation of
CEBPA become specific entity.
68. AML with myelodysplasia-related
changes
• The category of AML with myelodysplasia-related changes has
been retained
• The presence of multilineage dysplasia alone will not classify a
case as AML with myelodysplasia-related changes when a
mutation of NPM1 or biallellic mutation of CEBPA is present
• Cases lacking these mutations, the morphologic detection of
multilineage dysplasia (>50% dysplastic cells in at least 2 cell
lines) remains a poor prognostic indicator and is sufficient to
make a diagnosis of AML with myelodysplasia-related changes
69.
70. Therapy-related myeloid neoplasms
• Therapy-related myeloid neoplasms (t-MNs) remain as a
distinct category in the classification for patients who develop
myeloid neoplasms following cytotoxic therapy
• The t-MNs may be further subdivided as therapy-related MDS
or AML (t-MDS or t-AML), but the associated cytogenetic
abnormality, which is important for determining therapy and
prognosis, should be identified in the final diagnosis
• A number of t-MN cases have been shown to have germ line
mutations in cancer susceptibility genes; careful family
histories to uncover cancer susceptibility are warranted in t-
MN patients
71. AML, not otherwise specified
• Only a single change included in AML,NOS
• The subcategory of acute erythroid leukemia,
(erythroid/myeloid type) which was previously defined as a
case with >50% BM erythroid precursors and >20%
myeloblasts among non erythroid cells) has been removed
from the AML category
• In the new classification, myeloblasts are always counted as a
percentage of total marrow cells and the majority of such
cases have <20% total blast cells and are now classified as
MDS (usually MDS with excess blasts)
72.
73. Myeloid sarcoma
• Myeloid sarcoma remains in the classification as a unique
clinical presentation of any subtype of AML
• Myeloid sarcoma may present de novo, may accompany PB
and marrow involvement, may present as relapse of AML, or
may present as progression of a prior MDS, MPN, or
MDS/MPN
• Although listed separately in the classification, cases of
myeloid sarcoma without evidence of marrow disease should
be investigated comprehensively so that they can be classified
into a more specific AML subtype
74. Myeloid proliferations of Down syndrome
• The myeloid proliferations of Down syndrome include
1. Transient abnormal myelopoiesis (TAM)
2. Myeloid leukemia associated with Down syndrome
75. • Both are usually megakaryoblastic proliferations
• TAM occurring at birth or within days of birth and resolve in 1
to 2 months
• Myeloid leukemia occurs later, usually in the first 3 years of
life with or without prior TAM and persisting if not treated
• Both TAM and myeloid leukaemia associated with Down
syndrome are characterized by GATA1 mutations and
mutations of the JAK-STAT pathway, with additional mutations
identified in the myeloid leukaemia cases
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78. MCQs
1. Mastocytosis is classified under which
category?
A. Myeloproliferative neoplasms
B. Myelodysplastic Neoplasms
C. Myelodysplastic/Myeloproliferative
neoplasms
D. Myeloid Neoplasm as a separate entity
79. 2. The criteria for Accelerated Phase in revised
classification includes:
A. Clinical and morphological
B. Haematological and cytogenetic parameters
C. Evidence of resistance to TKI therapy
D. All the above
80. 3. Which one is not a diagnostic criteria of CNL:
A. No rearrangement of PDGFRA, PDGFRB, or
FGFR1, and no PCM1-JAK2 fusion
B. CSF3R T6181 or another activating CSF3R
mutation
C. Meeting WHO criteria for BCR-ABL1-positive
CML, PV, ET, or PMF
D. None of the above
81. 4. According to WHO 2016 Hemoglobi cut off for
diagnosing Polycythaemia Vera is:
A. Haemoglobin 18.5 g/dL in men
B. Haemoglobin 16.5 g/dL in women
C. Haemoglobin 16.5 g/dL in men
D. Haemoglobin 18.0 g/dL in women
82. 5. Which one is not the minor diagnostic criteria
for prefibrotic/early stage of PMF:
A. Anaemia not attributed to a comorbid
condition
B. Leukocytosis >11 x 109/L
C. Palpable splenomegaly
D. Leukoerythroblastosis
83. 6. Mutation not associated with Chronic
eosinophilic Leukaemia, NOS:
A. inv(16)(p13.1q22)
B. t(5;12)(q31-35;p13)
C. t(16;16)(p13.1 ;q22)
D. t(8;21)(q22;q22.1)
84. 7. Newly added category in Myeloid/lymphoid
neoplasms with eosinophilia and gene
rearrangement is
A. Myeloid/lymphoid neoplasms with PCM1-
JAK2
B. Myeloid/lymphoid neoplasms with PDGFRA
rearrangement
C. Myeloid/lymphoid neoplasms with PDGFRB
rearrangement
D. Myeloid/lymphoid neoplasms with FGFR1
rearrangement
85. 8. Criteria for CMML-0 category is:
A. <2% blasts in the blood and 5-9% in the bone
marrow; no Auer rods
B. < 2% blasts in the blood and < 5% in the bone
marrow; with Auer rods
C. < 2% blasts in the blood and < 5% in the bone
marrow; no Auer rods
D. <2% blasts in the blood and < 5-9% in the
bone marrow; with Auer rods
86. 9. Genetic criteria for JMML does not include:
A. Somatic mutation in PTPN11, KRAS or NRAS –
B. No Philadelphia (Ph) chromosome or BCR-
ABL1 fusion
C. Clinical diagnosis of neurofibromatosis type 1
or NF1 mutation
D. Germline CBL mutation and loss of
heterozygosity of CBL
87. 10. PML-RARA is associated with:
A. Myeloid proliferations associated with Down
syndrome
B. Acute myeloid leukaemia with recurrent
genetic abnormalities
C. Acute myeloid leukaemia with
myelodysplasia-related changes
D. Acute myeloid leukaemia, NOS