WBC Dissorders Flashcards
What are oncogenes?
Mutations in proto-oncogenes
-Genes that activate DNA replication
-Genes that activate cell division
-Genes that regulate commitment to differentiation and/or apoptosis
-“Gain of function” mutations
- growth factors
- growth factor receptors
- signal transduction proteins
- transcription factors
Dominant mutations (single allele)What are congenital causes of leukemia?
extra chromosomes
translocations
inversion
deletions
What are somatic causes of leukemia?
Radiation
Chemicals
Immunodeficiencies
What is acute leukemia?
Unregulated proliferation and accumulation of immature, malignant hematopoietic precursors
Occurs in bone marrow
Replaces normal bone marrow elements
What is leukemic hiatus?
Lots of immature cells and fully mature cells. No cells in between.
What is the complication of acute leukemias?
Immature leukemic cells accumulate bone marrow peripheral circulation spleen CNS Interferes with organ function and metabolic activity
What is leukostasis?
WBC counts exceeds 100,000/ µl Slowing of flow through capillaries Lungs - Hypoxia - Dyspnea Cerebrum - Stroke - Coma - Intracranial hemorrhage
What are metabolic problems in acute leukemia?
Rapid turnover of leukemic cells
Increased metabolic waste
- Uric acid, Gout, Kidney stones, Renal
failure
Hypercalcemia due to Abnormal parathyroid regulation
Cytokine activation of osteoclasts
- Localized bone reabsorption
Hyperkalemia due to lysis of fragile white blood cells and mechanical stress
What does the myeloperoxidase stain differniatate?
Myelo vs lymph
Primary granules in myelocytes stain
What is the non-specific esterase stain used for?
Stains for non-specific esterase enzyme in monocytic cells
What is the specific esterase used for?
Granulocytic blasts (AML) stain positive 1+ to 3+ Monocytic blasts (AMoL) negative
Blasts in acute myelomonocytic leukemia (AMML) stain 1+ to 2+
What is the Terminal Deoxynucleotidyl Transferase (TDT) used for?
Stains DNA polymerase found in immature lymphoid cell nuclei
Immunofluorescent assay
What is the M0 FAB classification?
Undifferentiated myeloblasts
3% of cases
MPO negative
What is the M1 FAB classification?
Myeloblast with minimal maturation
20% of cases
Minimal granulocytic cell maturation
At least 3% of blasts stain positive with MPO
What is the M2 FAB classification?
Myeloblast with maturation to or beyond the promyelocyte stage
>50% of the cells are MPO positive
Auer rods are common
t(8;21) has favorable prognosis
What is the M3 FAB classification?
APL or APML Abnormal promyelocytes Heavy granulation that packs the cytoplasm MPO strongly positive Associated with DIC t(15;17) is diagnostic for APL
What is the M4 FAB classification?
Myelomonocytic leukemia
Granulocytic AND monocytic differentiation
>20% of all nucleated cells
MPO, NSE and specific esterase positive
Gingival hyperplasia in 10% of patients
The bone marrow and circulating blood have variable amounts of differentiated granulocytes and monocytes.
What is the M6 FAB classification?
Erythroleukemia - Rare >50% of Marrow cells are erythroid Bizarre megaloblastic features Multinuclear, multilobular forms common CD71, glycophorin A positive
What is the M7 FAB classification?
Megakaryoblastic leukemia - Rare
Immature megakaryocytes
Distinguished by extensive fibrous tissue deposits (fibrosis) in the bone marrow.
What are the surface markers on B cells?
CD10 (CALLA), CD19, CD20, CD22
What are the surface markers on T cells?
CD2, CD3, CD5, CD7
What are the surface markers on myeloid cells?
CD13, CD15, CD33
What are the surface markers on myeloid cells?
CD14, CD36, CD64
What are the surface markers on HSC?
CD34, CD117
What is the surface marker for natural killer cell?
CD56
What are the characteristics of L1 ALL?
homogenous small blast
Nucleus is regular with scant cytoplasm
What are the characteristics of L2 ALL?
Hetergenous large blast
Irregular cleft and indentations in nucleou
Prominent nucleoli
Mod - abundant cytoplasma
What are the characteristics of L2 ALL?
Burkett’s lymphoma
Homogenous large blast
Regular nucleous with nucleoli
Abundant cytoplasm with vacuoles
