•Heterogeneous group of clonal hematological malignancies characterized by:
•PB cytopenias
•Dysplastic blood cells
•Propensity to transform into acute leukemia
•Almost always fatal
•No curative treatment other than allogeneic stem cell transplantation
•Myelodysplastic Syndromes (MDS)
•3 Sequential Phases of Apoptosis in MDS
•3 Sequential Phases
•Initiation
•Commitment
•Execution
•Factors that initiate apoptosis
•Chemotherapy and Radiotherapy
•Corticosteroids
•Growth factor deprivation
•Direct effect of cytotoxic T-cell activity
•Inhibitory Cytokines
•Tumor Necrosis Factor alpha (TNF-α)
•Transforming Growth Factor beta (TGF-β)
•Action of Fas-ligand on it’s receptor FAS/CD95
•MDS phenotype changes as the disease progresses towards leukemia
•Number of blast cells increases in the marrow
•PB leukocytosis may replace leukopenia
•Hepatosplenomegaly can occur
What type of anemia is most common in MDS?
Macrocytic, normochromic
What morphological abnormalities are helpful in the diagnosis of MDS?
Pseudo pelger huet, hypogranulation, ringed sideroblasts, micromegakaryocytes, monolobular megakaryocytes
What differentiates RAEB-t from AML of the M2 type?
the finding of t(8;21)
Which of these cell surface antigens is of prognostic significance in MDS?
CD19
CD HLA-DR
CD34
CD33
CD34
Which MDS subgroup has the most favorable prognosis?
RARS
What type of treatment may offer a cure in patients with MDS?
Allogeneic bone marrow transplantation
What type of agent may lead to secondary MDS (sMDS)?
Alkylating agents
Which is most likely to affect prognosis in MDS?
Leukopenia
Increased bone marrow myeloblasts
erythroid hyperplasia
thrombocytosis
Increased bone marrow myeloblasts
In female patients with RA and elevated platelets, what chromosome abnormality is most often found?
5q-
What genetic abnormality is important in MDS?
Chromosome deletions
What MDS scoring system is most widely used today?
IPSS
•Acceleration of MDS has been associated with:
•Decrease in medullary apoptosis
•Decrease in Fas expression
•Mutation at the p53 (tumor suppressor) and RAS (protooncogene) loci
Type I blast
•myeloblast of variable size, w/out azurophillic granules or Auer rods
type II blast
•myeloblast that is slightly larger and contain few azurophillic granules (1 to 20)
type I sideroblast
•normal siderblast containing 1 to 4 cytoplasmic iron-containing granules
type II siderblast
•considered abnormal, harboring 5 to 10 granules; scattered throughout the cytoplasm
Sideroblasts
•Dyserythropoiesis PB characteristics
•Anemia present in 90% of cases
•Erythrocyte Morphological Characteritics
•Anisopoikilocytosis
•Basophilic stippling
•Dual red blood cell population
•Pappenheimer bodies
•Dacrocytes,
•Fragmented cells
•Howell-jolly bodies
•Most difficult MDS to recognize and diagnose
•Dx relies mainly on subjective identification
•Lab Findings
•Anemia- more than 90% of patients
•Normochromic/macrocytic
•WBC- decreased
•Platelet-decrease
•<15% ringed sideroblasts in BM
•Erythroid hyperplasia common
Refractory Anemia
MDS subtype
•Dx rests on quantitative criteria:
•Presence of at least 15% ringed sideroblasts in the BM
•Ringed Sideroblasts
•Pathologic sideroblasts in which the usual migration of mitochondria from the nucleus does not occur
•Result: remain frozen around the nucleus, where insoluble iron conglomerates and further contributes to cell destruction
•Lab Features
•RBCs macrocytic or normocytic with dimorphic features
•Leukopenia
•Thrombocytopenia
2.Refractory Anemia w/ Ringed Sideroblasts (RARS)
What MDS subtype?
RARS
MDS subtype
•Degree of lineage dysplasia more significant
•Blasts ranges from 5% to 20%
•Dysgranulopoiesis with nuclear hyposegmentation and hypogranulation is frequent
•Thrombocytopenia
3.Refractory Anemia with Excess Blasts (RAEB)
RAEB
RAEB-t
CMML
•Interstitial deletion of the long arm of chromosome 5
•Classified as having RA; predominantly female
•Elevated platelet count, mild leukopenia
•5q- Syndrome
