SM_268: MDS Flashcards
Myelodysplastic syndrome is ___
Myelodysplastic syndrome is group of diseases caused by abnormal growth of abnormal-looking myeloid cells
- Myeloid neoplasm
- Myeloid cells: erythrocytes, granulocytes and monocytes, megakaryocytes
Describe myeloid neoplasms
Myeloid neoplasms
- Chronic myeloid leukemia and myeloproliferative neoplasms
- Acute myeloid neoplasms
- Myelodysplastic syndrome

Chronic myeloid leukemia and myeloproliferative neoplasms are ___
Chronic myeloid leukemia and myeloproliferative neoplasms are overgrowth of neoplastic myeloid cells in the bone marrow with full maturation and blood cytosis
Acute myeloid leukemia is ___
Acute myeloid leukemia is overgrowth of neoplastic myeloid precursors (blast) in bone marrow without maturation and circulating blasts in blood
Describe myelodysplastic syndrome
Myelodysplastic syndrome: group of clonal hematopoietic stem cell neoplasms characterized by
- Peripheral cytopenia: ineffective hematopoiesis in the bone marrow
- Morphologic dysplasia: abnormal looking cells in myeloid cell lines
- Risk of transformation to acute myeloid leukemia
In normal hematopoiesis, a myeloid stem cell undergoes ___
In normal hematopoiesis, a myeloid stem cell undergoes a series of ordered and well-controlled differentiation and maturation steps to produce mature blood cells
(RBCs, neutrophils, and platelets)
In myelodysplastic syndrome, ____ in a single stem cell ____ and confer a growth advantage
In myelodysplastic syndrome, genetic changes in a single stem cell disrupt normal maturation and confer a growth advantage
- Bone marrow is replaced by progenies of the abnormal stem cell
- Abnormal stem cells have deranged maturation and are not able to produce mature blood cells
In myelodysplastic syndrome, there is an increased degree of ___ within bone marrow precursors
In myelodysplastic syndrome, there is an increased degree of apoptosis within bone marrow precursors
- Ineffective hematopoiesis
- Anemia, neutropenia, and thrombocytopenia
- Disease worsens over time
- MDS patients eventually succumb to complications of cytopenia
Chronic myeloid leukemia and myeloproliferative neoplasm involves ____
Chronic myeloid leukemia and myeloproliferative neoplasm involves cytosis (< 20% blasts)
Acute myeloid leukemia involve ___
Acute myeloid leukemia involve increased blasts (> 20% blasts)
Myelodysplastic syndrome involves ___
Myelodysplastic syndrome involves cytopenia (< 20% blasts)
Myelodysplastic syndromes typically occur at age ___
Myelodysplastic syndromes typically occur at age 70
Describe risk factors for myelodysplastic syndrome
Myelodysplastic syndrome risk factors
- De novo (85%): etiology largely unknown, benzene and tobacco
- Therapy-related MDS (t-MDS): arises after treatment with chemo or radiation therapy
- Rare cases of familial MDS which are associated with germline mutations in RUNX1, CEBPA, GATA2, and other genes
- Some inherited disorders such as Fanconi anemia, dyskeratosis congenita have increased risk of MDS
- Acquired aplastic anemia is associated with increased risk of developing MDS
Describe clinical features of MDS
MDS clinical features
- Anemia: fatigue, SOB, chest pain, palpitations, dizziness, and syncope
- Neutropenia: recurrent or severe infection
- Thrombocytopenia: petechiae, bruising, bleeding
- Organomegaly is infrequent
- Slow-onset and long-standing
Describe diagnostic evaluation of MDS
Diagnostic evaluation of MDS
- Clinical history
- CBC and blood smear review: anemia, neutropenia, and thrombocytopenia
- Reticulocyte count: low
- Laboratory tests
- Iron studies: no iron deficiency
- B12, folate levels: normal
- Copper level: normal
- Bone marrow aspirate and biopsy (morphologic evaluation): dysplasia, blast count
- Cytogenetics: chromosomal aberrations
- Molecular studies: gene mutations
Describe MDS morphology
MDS morphology
- Hypercellular
- Erythroid hyperplasia (increased erythroid precursors)
- Dysplastic megakaryocyte

Describe erythroid dysplasia in MDS
Erythroid dysplasia in MDS
- Nuclear budding
- Internuclear bridging
- Multinucleation
- Bizarre nuclei
- Ring sideroblasts (iron)

Describe granulocytic dysplasia in MDS
Granulocytic dysplasia in MDS
- Hyposegmentation (pseudo Pelger-Huet)
- Hypogranularity

Describe megakaryocytic dysplasia
Megakaryocytic dysplasia
- Small and hypolobulated nuclei
- Separate nuclear lobes

Recurrent chromosomal abnormalities are more common in ____ than MDS
Recurrent chromosomal abnormalities are more common in treatment-related MDS than MDS
- -7 or del(71), del(5q),+8, i(17q) or t(17p), t(11q23;v)

Genetic aberrations in MDS involve ___
Genetic aberrations in MDS involve gain or loss of a chromosome or part of a chromosome
- Copy number changes in key genes may contribute to MDS
Describe del(5q) in MDS
Del(5q) in MDS
- Loss of long arm of chromosome 5 leads to haploinsufficiency in a number of genes including ribosomal protein RPS14: loss of one coppy of RPS14 causes ineffective erythropoiesis resulting in macrocytic anemia
- Haploinsufficiency of miR145 and miR146a in the 5q region may contribute to megakaryocytic abnormalities
Describe recurrent gene mutations in MDS
Recurrent gene mutations in MDS

Describe dyserythropoiesis in benign conditions
Dyserythropoiesis in benign conditions
- B12 / folate deficiency
- Exposure to heavy metals (arsenic)
- Copper deficiency
- Zinc deficiency
- Chemotheraoy
- Certain medications (isoniazid)
- Congenital dyserythropoietic anemia
Describe dysplastic neutrophils in benign conditions
Dysplastic neutrophils in benign conditions
- B12 / folate deficiency
- G-CSF
- Antibiotics: co-trimoxazone
- Immunosuppressants
- Chemo
MDS diagnosis requires that ____
MDS diagnosis requires that non-neoplastic causes of cytopenia and dysplasia have been ruled out, particularly if no cytogenetic abnormalities are present
Describe WHO classification of MDS
WHO classification of MDS
- MDS with single lineage dysplasia: BM < 5% blasts
- MDS with multilineage dysplasia: BM < 5% blasts
- MDS with ring sideroblasts: BM < 5% blasts
- MDS with isolated del(5q): BM < 5% blasts
- MDS with excess blasts
- MDS-EB-1: BM 5-9% or PB 2-4%
- MDS-EB-2: blasts 10-19% or PB 5-19%
Describe prognosis of MDS
MDS prognosis
- Heterogeneous, highly variable natural history
- Median survival of de novo: 9-29 months
- Median survival of therapy-related: 4-8 months
- Some have indolent course and live for more than 5 years
Describe morphologic risk groups of MDS
Morphologic risk groups of MDS
- Low risk: MDS with single lineage dysplasia, MDS with ring sideroblasts
- Intermediate risk: MDS with multilineage dysplasia, MDS withe xcess blasts-1 (5-9%)
- High risk: MDS with excess blasts-2 (10-19%)

___, ___, and ___ are most important prognostic factors for MDS
Blast count, cytogenetic abnormalities, and gene mutations are most important prognostic factors for MDS
MDS treatment depends on ___
MDS treatment depends on symptoms, risk scores, performance status, and other facvtors
- Asymptomatic low risk patients may be followed without treatment
- Symptomatic patients: supportive care, low intensity therapy, or high intensity therapy

Describe myelodysplastic syndrome with isolated del(5q)
Myelodysplastic syndrome with isolated del(5q)
- Women more commen
- Macrocytic anemia: normal or increased platelets
- Increased megakaryocytes with hypo- or unilobulated nuclei
- Median survival: 66-145 months
- Lenalidomide is effective
Describe MDS with excess blasts
MDS with excess blasts
- 40% of all MDS
- Cytogenetic abnormalities in 30-50%
- Prognosis: progressive bone marrow failure, progression to AML common, and median survival is 9-16 months
Summarize MDS
MDS
- Clonal hematopoietic stem cell neoplasm
- Affects older individuals
- Always has cytopenia
- Always has morphologic dysplasia
- Most important prognostic factors: percentage of blasts, cytogenetic abnormalities
- Likely due to acquired genetic aberrations that result in ineffective hematopoiesis