©2009 Mark Tuttle
Leukemia
Name
Mutation
Acute Lymphoblastic - L1: Small blasts (Tdt+)
Leukemia
- L2: Large blasts (Tdt+)
(ALL)
- L3: Peripheral B, Burkitt leukemia/lymphoma
o Tdt negative
Children <15 yrs
o Multiple vacuoles
o t(8;14), t(2;8), t(8;22), always 8  c-myc oncogene
Symptoms/Labs
- More than 20% blasts in marrow
- Lymphadenopathy
- CNS involvement (meningeal signs,
headache, vomiting) more common
in ALL than AML
- t(9:22) has worse prognosis than in
CML
Histology
Treatment
-
Acute Myelogenous
Leukemia
(AML)
- More than 20% blasts in marrow
- Neutropenia: bact infections, fever
- Anemia
- Thrombocytopenia: bleeding,
petechiae, epistaxis
- Maybe hepatosplenomegaly,
lymphadenopathy(in ALL)
- Bone pain
- Can be asymptomatic
- Auer rods clumps of
azurophilic granular materia
- 15-20% cure rate
15-40 year olds
Myelodysplastic
Syndrome
- M0: stem cells
- M1: w/o maturation, >90% blasts
- M2: with maturation, 20-90% blasts
o t(8;21) or t(16;16)  CFB blocks differentiation
- M3: acute promyolocytic leukemia APL, Auer rods ↑
o t(15;17)  PML blocks differentiation
o Treat with ATRA to promote differentiation
o Severe DIC due to dying PMN granules
- M4eo: eosinophils
o t(16;16)  same PML mutation as M2
- M4/5: Acute monocytic leukemia
o t(11q23;v)  same PML mutation as M2
- M6: Erythroleukemia
- M7: Megakaryocytic
o Myelofibrosis common
o Increased in kids w/down syndrome
- Commonly deletions
- Less than 20% blasts “pre- Pseudo Perger-Huet
leukemia”
neutrophils (2 nuclear lobes)
- 2-8 years post radiation or chemo is
common scenario]
- Also can be idiopathic
- Ringed Sideroblasts
- 1/3 die from
unrelated
- 1/3 die from
MDS
complications
- 1/3 die from
progression to
AML
- 1-3 yr prognosis
Name
Chronic Myeloblastic
Leukemia (CML)
Polycythemia vera
Essential
Thrombocytosis
Primary
Myelofibrosis
Chronic Lymphocytic
Leukemia (CLL) /
Small lymphocytic
leukemia (SLL)
The most common
leukemia in adults
Hairy Cell Leukemia
(HCL)
Multiple Myeloma
Waldenstrom’s
Macroglobulinemia
Mutation
Symptoms/Labs
- t(9;22) Philly chromosome in - Hypercellular marrow
100% of cases
- WBC > 50,000
- Basophils ↑, >20% in accelerated phase
- Massive splenomegaly
- LAP low (High in leukemoid rxn)
- Can be very high platelets
- Can transform to acute leukemia (blast crisis)
(2/3 transform to AML, 1/3 transform to ALL)
- Jak2 mutation in 95%
- Increased RBC mass, high Hb & Hct
- Low or undetectable EPO
- Need to rule out CO poisoning
- Increased blood viscosity
- Bleeding + thromboses with infarctions, DVD, strokes, Budd-Chiari
- Transforms to myeolfibrosis frequently with massive
splenomegaly
- Jak2 in 50%
- Bleeding & thromboses
- MPL in 10%
- Erythromelalgia (throbbing burning in hands & feet)
(Myeloproliferative
- Splenomegaly
leukemia gene)  works
with thrombopoitin gene
- Marrow fibrosis due to megakaryocytes cytokines
- Extramedullary hematopoisis
- Massive splenomegaly
- Immature myeloid cells in blood
- Dx by flow cytometry
- Nonspecific or asymptomatic
- CD5+, CD10-, CD23+
- Generalized lymphadenopathy frequent
- High WBC, absolute lyphocytosis
- Coombs+ hemolytic anemia = spherocytes
- Transform to prolymphocytic leukemia (in blood) or large cell
lymphoma (Richter syndrome in lymph node)
- Dx by flow cytometry
- Triad: Older male, massive splenomegaly, pancytopenia
- Bone marrow dry tap
- TRAP+ cells
- IL-6 driven proliferation  Bone resorption
- Usually IgG (not filtered by kidney, no kidney problems)
- Need >10% Plasma cells in marrow or is MGUS (uncertain signif)
- Hypercalcemia
- Bence-Jones proteinuria
- Can get primary amyloidosis if chains depositing in organs
- IgM always  kidney problems
- No bone lesions
- Lymphadenopathy, Reynaud’s phenomenon, Hyperviscosity
Histology
- Teardrop RBCs
Treatment ©2009 M.T.
- Gleevac
(imatinib) targets
abnormal
tyrosine kinase
-
-
- Giant platelets
-
- Teardrop RBCs
-
- Smudge cells
-
- Fuzzy cytoplasm
-
- Blood rouleaux
- Poor prognosis
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