86 Myelodysplastic Syndromes Flashcards
Most common blood abnormality in MDS
Macrocytic anemia
Refers to the abnormal morphology that can be observed in neoplastic mature blood cells and maturing marrow erythroid, granulocytic, and megakaryocytic precursor cells, and is one of the distinguishing characteristics of MDS.
Dysplasia
TRUE OR FALSE
MDS can be diagnosed without dysplasia.
TRUE
MDS can be diagnosed without dysplasia.
Dysplasia is helpful for diagnosis, but is an epiphenomenon of driver mutations causing clonal expansion and cytopenias, and in the presence of excess blasts or certain chromosomal abnormalities, MDS can be diagnosed without dysplasia.
TRUE OR FALSE
The majority of MDS cases are age-related without a clear precipitating factor or any family history.
TRUE
The majority of MDS cases are age-related without a clear precipitating factor or any family history.
WHO 2016 MDS subtypes
(a) MDS with unilineage dysplasia (MDS-ULD) alone, or with ring sideroblasts (MDS-ULD-RS);
(b) MDS with multilineage dysplasia, again with or without ring sideroblasts (MDS-MLD-RS);
(c) MDS with isolated del(5q);
(d) MDS with excess blasts, type 1 or type 2 depending in the proportion of marrow or blood blasts (MDS-EB1 and MDS-EB2); and
(e) unclassifiable MDS
Some patients diagnosed with MDS may have their diagnosis change to CMML once their monocyte count exceeds ________.
1 × 109/L
The median age at MDS diagnosis in the United States is
70 years
TRUE OR FALSE
Onset of MDS before the age of 50 years is uncommon, except in patients with a germline predisposition or those patients who have received irradiation or cytotoxic chemotherapy for another malignancy
TRUE
Onset of MDS before the age of 50 years is uncommon, except in patients with a germline predisposition or those patients who have received irradiation or cytotoxic chemotherapy for another malignancy
(Males/Females) are affected with MDS up to 1.5 times
Males
With the exception of MDS with isolated ____for which there is a female predominance
del(5q)
Risk factors for MDS
Benzene (exposure of ≥40 parts per million [ppm]-years)
Cigarette smoking
Family history of myeloid malignancy
Chemotherapeutic agents, particularly alkylating agents and topoisomerase inhibitors
Radiation
The mechanism of therapy-related MDS
Promotion of expansion of a preexisting small TP53 or PPM1D mutant hematopoietic clone during marrow stress
Mutation associated with a familial platelet disorder with predisposition to AML (FPDAML)
RUNX1
Syndrome comprising MDS, verrucae, and congenital lymphedema
Emberger syndrome
(GATA2)
Syndrome comprising monocytopenia and nontuberculous mycobacterial infections
MonoMAC syndrome
(GATA2)
The hallmark of clonal hematopoiesis in MDS is the
Presence of a somatic genetic abnormality
Percentage of patients with MDS will have a grossly abnormal karyotype
50%
The most common somatic genetic lesions in MDS
Mutations of individual genes
Most common mutated gene in MDS
SF3B1
TET2
The only somatic mutations associated with a favorable prognosis.
Strongly associated with ring sideroblasts
SF3B1
Associated wit del(20q)
U2AF1
Mostly in men X-linked
ZRSR2
Associated with ATMDS (acquired thalassemia and myelodysplastic syndrome)
ATRX
Rarely translocated in MDS
ETV6
Associated with complex karyotypes
TP53
Enriched in MDS-RS-T/MDS with ring sideroblasts and thrombocytosis
JAK2
The most frequent chromosomal abnormalities seen in MDS, present in nearly half of all patients, are
Deletions of chromosomal segments or loss of entire chromosomes (monosomies)
The most common karyotypic abnormality observed in MDS
Del(5q)
Occurring in approximately 15% of patients
Syndrome characterized by dyserythropoietic anemia, micromegakaryocytes with a normal or elevated platelet count, female predominance, and lower risk of transformation to AML
5q-minus syndrome
Occur more frequently (~50%) in patients with prior exposure to alkylating agents
Monosomy 7 and Del(7q)
This is the only large-scale amplification frequently encountered in MDS, present in approximately 5% of patients.
Trisomy 8
Intermediate prognosis
Nonspecific as it can occur in patients with MPN, AML, or aplastic anemia
Sometimes observed in individuals with immune thrombocytopenia or without any hematologic disorder
An isolated lesion it is associated with disease risk comparable to that of MDS patients with normal karyotypes.
Del(20q)
Not a pathogenic lesion in MDS, but instead an age-related event that can occur in men without cytopenias, akin to CHIP
Loss of Y
Genetic abnormalities identified in elderly patients without cytopenias and are considered pathogenic lesions in MDS
Teneleven translocation 2 (TET2) and DNMT3A
Patients with chromosome 17 abnormalities typically have a poor prognosis, particularly in the presence of a ______ mutation.
TP53
Chromosome 17 Abnormalities Including del(17p) can co-occur with mutations of _______, abnormalities that are found more often in patients with both dysplastic and proliferative disease features
SETBP1
Complex karyotypes are defined as
Having three or more cytogenetic abnormalities of any sort and are strongly associated with an adverse prognosis
The most frequent abnormalities seen in both monosomal and complex karyotypes involve chromosomes ________
Chromosomes 5 and 7
Approximately 50% of patients with complex karyotypes have a concomitant ______mutation and account for the majority of patients with mutations of this gene.
TP53
The most frequently mutated class of genes in patients with MDS encode _________ proteins involved in the excision of introns and the ligation of exons from maturing pre-mRNA strands.
Splicing factor proteins
The most frequently mutated splicing factor gene and encodes the U2 small nuclear riboprotein complex subunit responsible for branch site recognition
Very tightly associated with the presence of ring sideroblasts
SF3B1
