Leukemias (AML/ALL)

What are the acute/precursor leukemias?

• AML

• ALL

What are the Chronic leukemias

• CML

• CLL

• MDS

• MPD

What is the definition of leukemia?

• progressive, malignant disease of hematopoietic system

• characterized by unregulated proliferation of one cell type

What is the etiology of leukemia?

Idiopathic

• activation of oncogenes

• inadequate tumor suppressor gene

• inappropriate epigenetics

What are proto-oncogenes?

Cause cells growth, genetic transformation of proto-oncogenes results in oncogenes

What do tumor suppressor genes do?

Function to inhibit cell growth in normal cells

What does epigenetics affect?

The availability of genes to be expressed

What happens with acute forms of leukemia?

• 50% of all leukemias

• aggressive

• sudden onset

• immature cells

• AML and ALL

• infection/bleeding

What happens with chronic forms of leukemia?

• less aggressive

• insidious onset

• more mature cells

• adults

What is the clinical course of acute leukemia?

• fatigue

• pallor

• petechiae/bruising

• fever

• bone pain

• neurologic abnormalities

What is the typical lab presentation of AML?

• N/N anemia

• decreased plt count

• variable wbcs

• see blasts, leukemic hiatus and auer rods

• increased uric acid and LD

What is typical of the bone marrow in AML?

• hypercellular

• increased M:E ratio

• ± dry tap

• usually 1 cell line predominates

What is FAB classification system of AML based on?

• morphology and cytochemistry

• >30% blast in bone marrow

What is the who classification of AML based on?

• morphologic

• immunophenotype

• molecular analysis

• >20% blasts

What are the six subtypes of the WHO classification system of aml?

1. AML with recurrent genetic abnormalities

2. AML with myelodysplasia-related changes

3. Therapy-related myeloid neoplasms

4. AML no otherwise specified by the preceding subgroups

5. Myeloid sarcoma

6. myeloid proliferations related to Downs syndrome

What is M0?

• Myeloblastic without differentiation

• >=90% blasts

• positive stains

  • MPO/SBB (<3%)

  • specific esterase

  • PAS

What is M1?

• Myeloblastic without differentiation

• >=90% blasts

• ± auer rods

• Positive stains

  • MPO/SBB (>3%)

  • Specific esterase

  • PAS

What is M2?

• Myeloblastic with differentiation

• 30-89% blasts

• 10% promyelocytes and myelocytes

• ± auer rods

What is M3?

• Promyelocytic

• >30% blasts

• Increased promyelocytes

• auer rods

• Associate with DIC

• Hyper and micro granular variant

What chromosomal translocation is associated with AML M3?

15/17

What is M4?

• Myelomonocytic

• >30% blasts

• Increased monocytes

• positive stains

  • MPO/SBB

  • Specific esterase

  • PAS

  • Non-specific esterase

What is M4e?

• Same appearance as M4

• Increased eos in bone marrow

• Inversion of chromosome 16

What is M5?

• Monocytic

• >30% blasts

• >80% monocytes

• blasts, promonocytes, monocytes

• associated with tissue infiltrates

What is M5a?

Where monoblasts predominate

What is M5b?

Where promonocytes predominate

What is M6?

• erythroleukemia

• Digugliemo’s syndrome

• >30% blasts

• >50% RBC precursors

• least common acute leukemia

• Often evolves from M1 or M2

What is M7?

• megakaryoblastic

• >30% megakaryoblasts

• increased fibrin and reticulin in bone marrow, dry tap

• associated with down’s syndrome

• platelet blebbing

What methods can be used to differentiate AML?

1. Cytochemical stains

2. Bone marrow stains

3. Immunophenotyping

4. flow cytometry

5. cytogenetics

6. PCR

What are the WHO classifications of ALL?

• B cell ALL with gene or chromosome changes

• B-cell ALL, not otherwise specified

• T-cell

• ALL of ambiguous lineage

What is the FAB classification of ALL?

• L1 T cell or pre-B cell: cell small and uniform

• L2 T cell or pre b cell: cells large and varied

• L3 B cells: cells large and varied with vacuoles

What is L1?

• small, homogenous cells

• fine chromatin

• no nucleoli

• scant cytoplasm

• most common in children

• best prognosis

What is L2?

• large cells

• fine chromatin

• irregular nuclei with clefts

• nucleoli

• abundant cytoplasm

• adults

What is L3?

• large cells

• fine chromatin

• nucleoli

• very blue and vacuolated cytoplasm

• burkitt’s lymphoma

What do immature lymphs stain with?

TdT

What are the cell markers/cytochem stains of T-cells?

• CD 1,2,3,4,5,6,7

• acid phosphates positive

What are the cell markers/cytochem stains of B cells?

• CD 10, 19, 22

• sIg positive

What are the REAL classifications of ALL?

• B cells

• T/NK cell

• Hodgkin’s disease

What does a 8:21 translocation indicate?

Better prognosis for AML

What are PCR techniques important in the diagnosis of?

• sickle cell anemia

• CML

• AML-M3

• ALL

• Lymphoma

• Factor V Leiden

What are some other lab considerations is Leukemia?

• Albumin smears

  • increased number of smudge cells

  • increased hct

• Buffy coat smears

  • used with low wbc counts/abnormal cells

What are the phase of leukemia therapy?

• induction

• CNS prophylaxis

• maintenance/consolidation

What are the side effects of leukemia therapy?

• kills all fast-growing cells (hair, skin, GI)

• Bone marrow suppression

• increased cell turnover (kidney failure from increased cell turnover)