Leukemias and Cytogenetics

Monophyletic theory

all blood cells are derived from a single pluripotent HSC

apoptosis

programmed cell death

necrosis

accidental cell death

erythropoiesis

RBC production that occurs primary in the bone marrow and is stimulated by EPO

leukopoiesis

WBC production in the bone marrow, giving rise to various leukocyte lineages that aid in immune defense

myelopoiesis

type of leukopoiesis, involving the formation of myeloid cells, granulocytes, monocytes from myeloid stem cells in the bone marrow

lymphopoiesis 

production of lymphocytes from lymphoid progenitor cells that occurs in the bone marrow or lymphoid tissues 

megakeryopoeisis

platelet production form megakaryocytic in the bone marrow

cellular immunity

adaptive immune response mediated by T-lymphocytes that directly attack and destroy infected or abnormal cells

innate immunity 

nonspecific first line of defense that is present at birth and responds quickly to pathogens 

humoral immunity

adaptive immunized mediated by B-lymphocytes that diff into plasma cells to produce antibodies that target specific antigens

Chemotaxis

neutrophil recruitment to the inflammatory site caused by chemotaxis agents released

integrins

receptors that mediate attachment between cells and tissue to help in cell signaling 

housekeeping

removal of debris and dead cells

basophil function

initiate and modulate allergyc inflammations, help combat helminth infections

eosinophil 

antigen presenting cells 

mast cell

APC’s that modulate allergic inflammations

monocyte

innate and adaptive immunity, housekeeping

B cell 

humoral immunity, Ab production, and Ag presentation to T cells 

T cells

cellular immunity, regulating immune response, killing target cells directly

NK cells

innate immunity, killing tumor and virus-infected cells without prior sensitization

Pelger huet 

band form, “bikini top or dumbell” round or oval nuclei 

cause of pelger Huet 

failure of segmentation of granulocyte nuclei 

May Hegglin

dohle like inclusions, myosin heavy chains, thrombocytopenia, giant platelets 

alder-reilly

prominent dark metachromic granules in neutro. basos, monos, and/or lymphs, resembles toxic granulation and does not affect WBC function

cause of alder-reilly

granules are formed by the accumulation of partially degraded mucopolysaccharides in lysosomes

Chediak-Higashi in lymphocytes

moderately coarse to large azurophilic red/purple granules 

Chediak-Higashi in neutrophils

moderately coarse to large azurophilic gray/blue granules

Chediak-higashi cause 

defective granulation and abnormal membranes of abnormal lysosomes 

hypersegmentation

>5 lobes in a poly or >6 poly with multiple lobes

auer rods

red staining rods found in the cytoplasm of malignant myeloblasts or promyeloblasts and composed of primary granules

reactive lymphocytes

large, chromatin less clumped, nucleus cleft or left out, cytoplasm is basophilic patchy foamy indented by RBCs and may have vacuoles “ballerina skirt”

Smudge cell

nuclear remanent of lymphocyte, basket cell and no discernible cytoplasm

principle of monospot antibody test 

heterophiles antibodies agglutinate horse erythrocytes 

toxic granulation

dark blue/purple cytoplasmic granules in metamyelocytes, bands, or segs with primary granules

Dohle bodies

small oval, pale blue inclusions in the peripheral cytoplasm of segs and bands in singles or multiples (composed of RNA)

hyposegmentation 

absent or decreased number of granules in neutrophils occurring naturally 

vacuolization

presence of vacuoles in the cytoplasm of neutrophils

comrade

vacuolization, toxic granulation, and dohle bodies seen together in infections, poisoning, chemotherapy

histoplasma capsulatum 

fungus found in Ohio and Mississippi River and seen in the cytoplasm of leukocytes 

loa loa

filarial nematode most common in Africa and India

Trypansoma gambiense

linked to African sleeping sickness

Babesia species 

protozoan blood parasite that appears like malaria, absence of crescent gametocytes

Plasmodium falciparum

protozoan parasite that is the cause of malaria, rings and crescent shape gametocytes

Leukocytosis

WBC >11.5 × 10⁹

Leukopenia

WBC <4.5 × 10⁹

Leukemia reaction 

WBC >50 × 10⁹ with marked left shift 

leukoerthroblastic reaction

presence of immature RBCs and granulocytes together

neutrophilia

>8.1 × 10⁹

neutropenia 

<2.3 × 10⁹

eosinophilia

0.6 × 10⁹ or >600/mm³

basophilia

0.2 × 10⁹ or >200/mm³

monocytosis 

> 1.2 × 10⁹

lymphocytosis in children

>11.1 × 10⁹

lymphocytosis in adults

>4.8 × 10⁹

lymphopenia in children 

<1.5 × 10⁹

lymphopenia in adults

< 0.8 × 10⁹

shift to the left

immature cells in the PB

inverse ratio

more lymphocytes than neutrophils 

serve neutropenia

<1.5 × 10⁹ with increased risk of infection

more severe neutropenia

<1.0 × 10⁹ with increased risk of auto-infection

Most severe neutropenia 

<0.5 × 10⁹ with very serious risks of reverse isolation and prophylactic antibiotics 

FISH 

molecular cytogenetic technique used to detect and localize specific DNA sequences on chromosomes 

Chronic granulomatous disease 

genetic mutation where phagocytes are unable to produce superoxide and reactive oxygen species 

Where are integrins found

on white blood cells

where are selectins found 

on endothelial cells 

Type 1 LAD

mutation in reduced or defective B2 integral subunits (CD18) found on leukocytes

lysosomes 

membrane bound structures present in cytoplasm of most cells 

lysosomal storage disorders

errors in metabolism in which enzyme deficiencies allow the accumulation of products of cellular metabolism within lysosomes

oncogene

genes that cause dominant-acting cancer mutations(malignancy)

proto-oncogene 

code for a protein found in normal cell cycle regulation 

tumor suppressor gene

code for proteins that help cells resist malignant transformation

chemotherapy

oral or parenteral cancer treatment with compounds that have anti tumor properties

radiation therapy 

use of ionizing energy to kill malignant cells by damaging DNA 

supportive therapy

use of pharmaceuticals to manage symptoms of malignancies and malignancy treatments

target treatment

type of medication that blocks growth of cancer cells by interfering with specific targeted molecules

HSC transplant 

replacement of the patients HSC 

Allogenic HSC transplant

donor is genetically different than the patient

Autolous HSC transplant

patient’s own stem cells are used

haploid 

n or 23 

euploid/diploid

2n or 46

polyploid

multiple of n

triploidy 

3n or 69

tetraploidy

4n or 92 

aneuploidy

gain or loss of chromosomes

lypodiploid

less than 46

near haploid 

23-24 

pseudohaploid

cells with 46

derivative chromosomes

chromosome with a translocation

leukemia 

clonal proliferations of malignant leukocytes that arise in the BM before dissemination to PB, lymph nodes, and organs 

deletions

interstitial deletions involved two break and the loss of a segment between breaks

terminal deletions

only involves one break

translocations 

occurs only in Afrocentric chromosomes and results in the fusion of two chromosomes 

insertions

rare because 3 separate breaks are required

isochromosome

division of chromosomes is perpendicular to their long axis instead of parallel

ring chromosome 

results from the breakage and rejoicing of the ends of a chromosome(partial monosomy) 

paracecntric inversion

does not include the centromere

pericentric inversion

includes the centromere

Primary/stem line aberration 

aberration frequently as the sole karyotype abnormally associated with a particular tumor 

Secondary/Sideline aberration

aberration that is never found alone and develops in cells already carrying a primary aberration