82 Classification and Clinical Manifestations of the Clonal Myeloid Disorders Flashcards
Refers to the relationship of the disease in question to normal cellular differentiation and maturation and the regulation of cell population homeostasis (birth and death rates)
Deviation
Clonal hematopoiesis as a result of a somatic mutation in a clone of marrow cells, but marrow and blood cells without any phenotypic evidence of a blood cell disorder, that is, normal marrow and blood cell morphology and normal blood cell counts.
CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP)
A somatic mutation in which an unequivocally abnormal cytopenia is or cytopenias are present
Clonal cytopenia of unknown significance (CCUS)
Definition of cytopenias in clonal cytopenia of unknown significance (CCUS)
Hemoglobin :
Absolute neutrophil count :
Platelet count :
Hemoglobin : <100 g/L
Absolute neutrophil count : <1.8 × 10 9 /L
Platelet count : <100 × 10 9 /L
A somatically mutated clonal disorder without a phenotype but with more concerning somatic mutations
Clonal hematopoiesis of oncogenic potential (CHOP)
**In the case of CHOP, the mutations are disease-related or even disease-specific mutations and have a higher propensity to undergo clonal evolution to a progressive neoplasm.
TRUE OR FALSE
In the cases of CHIP and CHOP, the definition includes absence of evidence of paroxysmal nocturnal hemoglobinuria or clonal lymphocytosis or cytologic dysmorphia.
TRUE
In the cases of CHIP and CHOP, the definition includes absence of evidence of paroxysmal nocturnal hemoglobinuria or clonal lymphocytosis or cytologic dysmorphia.
Most frequent specific gene mutations which make up about 75% of CHIP
DNMT3A, TET2, ASXL1, and JAK2
Mutations that are more frequently detected in secondary AML, following MDS or CMML
TET2
ASXL1
Associated with deletions in the long arm of chromosome 11 and with the presence of ring sideroblasts in MDS.
SF3B1
The variant allele frequency (VAF) by definition is above ____ %
Above 2%
TRUE OR FALSE
Age-related clonal hematopoiesis (ARCH) is in essence a synonym for CHIP but denotes the effect of aging
TRUE
Age-related clonal hematopoiesis (ARCH) is in essence a synonym for CHIP but denotes the effect of aging
The rate of progression of CHIP to a clinically evident neoplasm is approximately 0.75% of affected persons per year, of which the majority are __________ neoplasms
Myeloid neoplasms
TRUE OR FALSE
A coexisting significant finding in patients with CHIP is a predisposition to cardiovascular morbidity and mortality.
TRUE
A coexisting significant finding in patients with CHIP is a predisposition to cardiovascular morbidity and mortality.
The vascular occurrences in CHIP may relate to the mutations of genes such as __________
TET2 and JAK 2
Defined as an idiopathic cytopenia(s) without a detectable somatic mutation.
Idiopathic cytopenias of undetermined significance (ICUS)
Diseases include one group in which late precursor apoptosis (ineffective myeloproliferation) is characteristic (the clonal cytopenias) and one group in which proliferation is exaggerated and cellular maturation approximates normal (effective myeloproliferation)
MODERATE-DEVIATION CLONAL MYELOID DISEASES
Essential characteristic of moderate-deviation clonal myeloid diseases
Cytopenias resulting from exaggerated apoptosis of marrow late precursors (referred to as “ineffective hematopoiesis”)
Variable dysmorphogenesis of blood cells
The blood cell abnormalities, characteristic of the clonal cytopenias and oligoblastic myelogenous leukemia, include abnormalities of:
(a) red cell size (macrocytosis, anisocytosis), shape (poikilocytosis), and cytoplasm (basophilic stippling, pathologic sideroblasts);
(b) neutrophil nuclear or organelle structure (cytoplasmic hypogranulation, nuclear hypolobulation or hyperlobulation, and condensation)
(c) platelet variation in size (megathrombocytes) and granulation (hypogranulation or abnormal granulation)
Blast percentage in:
AML:
MDS:
Blast percentage in:
AML: 20% or more
MDS:5%–20%
**The use of an arbitrary boundary of 20% blasts has no pathobiologic basis.
TRUE OR FALSE
In severe inflammatory states with leukemoid reactions, the marrow myeloblast percent is usually increased .
FALSE
In severe inflammatory states with leukemoid reactions, the marrow myeloblast percent is usually DECREASED because in this circumstance, precursor cell expansion in the myelocyte pool is far greater, such that the percent of blast cells decreases.
TRUE OR FALSE
Three percent or 4% blast cells in the marrow at the time of presentation, after therapy, or suspected relapse should not be considered “normal” and is evidence of leukemic hematopoiesis.
TRUE
Three percent or 4% blast cells in the marrow at the time of presentation, after therapy, or suspected relapse should not be considered “normal” and is evidence of leukemic hematopoiesis.
TRUE OR FALSE
Polycythemia vera and essential thrombocythemia show morphologic evidence of leukemic hematopoiesis
FALSE
Polycythemia vera and essential thrombocythemia DO NOT show morphologic evidence of leukemic hematopoiesis; the proportion of blast cells in the marrow is never increased above normal, and blast cells are never present in the blood.
Percentage of Janus kinase 2 (JAK2) gene mutation in:
PV:
ET:
PV: 95%
ET: 50%
Other mutations in ET aside from JAK2
Wild-type JAK2 gene
Calreticulin (CALR) gene
Myeloproliferative leukemia virus gene (MPL)
The most constant feature in primary myelofibrosis
Abundance of neoplastic, dysmorphic megakaryocyte
** The megakaryocytic abnormalities are so dominant and consistent in this disorder that it could be considered chronic megakaryocytic leukemia
Gene mutations in PMF
JAK2 gene (50%)
CALR gene
MPL mutation
Percentage with “triple negative” mutation in PMF
10%
Cause of fibrosis in PMF
Cytokines released by neoplastic (leukemic) megakaryocytes
Gene mutation in CML
translocation t(9;22) (q34;q11)(BCR-ABL1 [Abelson murine leukemia viral oncogene homologue 1])
Percentage of patients with CML with t(9;22) mutation
90%
Percentage of CML patients do not have the rearrangement
4%
Primary myelofibrosis terminates in acute leukemia in approximately _____% of patients.
15%
TRUE OR FALSE
Therapy is required in all cases of CML and primary myelofibrosis at the time of diagnosis.
FALSE
Therapy is required in all cases of CML, and in most, but not all, cases of primary myelofibrosis at the time of diagnosis.
Gene mutation in Chronic neutrophilic leukemia
Colony-stimulating factor 3 receptor gene (CSF3R) 30%
CSF3R and a SET binding protein gene (SETBP1) mutation 60%
JAK2 V617F mutation 10%
Previous name of Chronic eosinophilic leukemia
Hypereosinophilic syndrome with evidence of clonal hematopoiesis involving eosinopoiesis
Gene mutation in Chronic eosinophilic leukemia
PDGFR-β gene
PDGFR-α gene (FIP1L1–PDGFR-α fusion gene)
