Myeloid Neoplasms Flashcards
Give rise to common myeloid stem cell or common lymphoid stem cell
Multipotent stem cell
Cannot self renew, but actively differentiate
Blasts
AML
Acute myeloid leukemia
Acquired genetic alterations causing impaired maturation of leukemic cells
AML
Include RUNX1, RARA, and NPM1 mutations
AML
Includes mutations of genes involved in signal transduction
FLT3, JAK2, and KIT
AML
Has auer rods. Myeloperoxidase positive.
CD34/CD13/CD33
Myeloblast of AML
Myeloperoxidase negative
CD11b/CD14/HLADR
monoblast
Associated with t(8;21), inv16, t(15;17), and t(11q23)
AML
Formation of chimeric gene with dominant negative activity. Interferes with fn of transcription activator, so have daughter cells unable to differentiate
inv 16 of AML
t(15;17) causes
acute promyelocytic leukemia
of AML
RARA gene fused to PML gene. PML/RARA protein blocks ___________ differentiation at _____________ stage
Translocation?
myeloid
promyelocytic stage
t(15;17)
Use topoisomerase inhibitors (1-3yr latency), alkylating agents (5-7 yr latency). Poor prognosis
AML
Similar symptoms to ALL. BM failure. Bleeding diathesis. Opportunistic infections. Granulocytic sarcoma
AML
Associated with DIC
Acute promyelocytic leukemia
t(15;17) acute promyelocytic leukemia is different - use _______ based chemo plus _______ or ________
Anthracylcine
ATRA
Arsenic
ATRA
All trans retnoic acid (vit A analogue)
t(8;21) and inv 16
Better prognosis
11q23
poorer prognosis
Refractory anemia only is _____ grade
low
Refractory anemia with excess blasts is ____ grade
high
Clonal multipotent stem cell abnormality resulting in ineffective hematopoiesis with dysplasia
myelodysplastic syndromes
Symptoms related to cytopenias. Therapy related - occurs after chemos
myelodysplastic syndromes
Panycotpenic with macrocytic anemia. Dysplastic neutrophils.
Trilineage hyperplasia with dysplasia in at least one line
Myelodysplastic syndromes
Monosomy 5 and 7
del5q, del7q, del20q
tri 8
Myelodysplastic syndromes
Effective hematopoiesis, just too much of it.
Multipotent stem cell abnormality giving rise to all myeloid lines.
Chronic myeloproliferative diseases
CMPD
Chronic myeloproliferative diseases
Neoplastic cell is pluripotent giving rise to myeloid and lymphoid lines
CML
Marrow hypercellularity with increased peripheral counts.
Genetic abnormalities have tyrosine kinase activity
chronic myeloproliferative disorders
Can have extremedullary hematopoiesis
Chronic myeloproliferative diseases
Pluripotent stem cell abnormality.
t(9;22) BCR-ABL fusion
Tyrosine kinase activity
CML
Leukocytosis and neutrophilia with left shift.
Eosinophils and basophilia.
thrombocytosis 50% time
CML
Packed BM with prominent granulocytic hyperplasia.
Seablue histiocytes due to increased cell turnover
Small dwarf megakaryocytes
CML
Middle age
Extramedullary hematopoeisis causes LUQ pain and fullness
Slow progression to AML/ALL without treatment
CML
Treat with tyrosine kinase inhibitor gleevac
CML
Must rule out secondary polycythemia
Decreased serum erythropoietin
Multipotent stem cell (erythro, leuko, and thrombocytosis)
Jak2 mutation
polycythemia vera
PV
polycythemia vera
See erythrocytosis in PB
Hypercellularity in BM with trilineage hyperplasia
Minimal reticulin fibrosis
Late stage BM can become spent
PVV
Late middle age.
Vascular consequences from increased RBC mass
Abnormal blood flow on venous side with stagnation/thrombosis
DVT, abnormal plt function
PV
Least common of CMPDs. Older >60 usually
Platelet count >600K with abnormal large platelets
Diagnosis of exclusion
Essential Thrombocyothemia
ET
Essential Thrombocythemia
Asymptomatic.
Dysfn and numerous plts. Causes bleeding and thrombosis.
Unusual sites of thrombosis.
Symptoms related to microvascular thrombosis
ET
Hypercellularity with huge megakaryocytes.
Indolent
Essential thrombocythemia
Increased reticulin and collagen fibrosis.
Spent marrow and extramedullary hematopoeisis
Primary myelofibrosis
Neoplastic megakaryocytes release PDGF and TGF-b
JAK2 mutation 50% time
Primary myelofibrosis
Hypercellular marrow with trilineage hyperplasia
Megakaryocytes are large and dysplastic
Minimal fibrosis
Prefibrotic of primary myelofibrosis
Hypocellular marrow with replacement by fibrosis.
Atypical clusters of megakaryocytes
Leukoerythroblastosis with marked erythrocyte anisopoikilocytosis and nRBCs
Fibrotic of primary myelofibrosis
Usually in people >60
Fatigue with progressive anemia
Primary myelofibrosis
Must differentiate and self renew. Greatest capacity for self renewal
Pluripotent stem cells
Leukocytosis and absolute eosinophilia.
Fusion of PDGFRalpha and FIP1LI1
Pts respond to gleevac
Chronic eosinophilic leukemia/hypereosinophilia syndrome
