12 white blood cell disorders

12 White Blood Cell Disorders

Benign Qualitative White Blood Cell (WBC) Disorders

Pathogenesis

1. Defects in leukocyte structure o Example-membrane fusion defect in Chédiak-Higashi syndrome

2. Defects in leukocyte function

a. Leukocyte adhesion defect Example-deficient selectin or CD11a/CD18

b. Phagocytosis defect Example-decreased opsonins in Bruton's agammaglobulinemia

c. Microbicidal defect

Example-deficiency of myeloperoxidase

Benign Qualitative White Blood Cell (WBC) Disorders

Pathogenesis







Pathogenesis







Clinical findings

1. Unusual pathogens (e.g., coagulase-negative Staphylococcus) 2. Frequent infections and growth failure in children 3. Lack of an inflammatory response (e.g., production of "cold" abscesses)

4. Severe gingivitis

Job's syndrome is an autosomal recessive disorder of neutrophils, characterized by abnormal chemotaxis leading to "cold" soft tissue abscesses due to Staphylococcus aureus. Patients have red hair, a leonine face, chronic eczema, and increased IgE (hyperimmune E syndrome).

Unusual benign leukocyte reactions1. Leukemoid reaction

a. Absolute leukocyte count usually above 50,000/μL. May involve neutrophils, lymphocytes, or eosinophils

b. Etiology

.i Perforating appendicitis (neutrophils)

.ii Whooping cough (lymphocytes)

.iii Cutaneous larva migrans (eosinophils) b. Pathogenesis

Exaggerated response to infection .. Leukoerythroblastic reaction

a. Immature bone marrow cells enter the peripheral blood b. Pathogenesis

.i Bone marrow infiltrative disease

.ii Examples-fibrosis, metastatic breast cancer b. Peripheral blood findings

.i Myeloblasts, progranulocytes

.ii Nucleated RBCs, tear drop RBCs

Benign Quantitative WBC Disorders

Disorders involving neutrophils page 228

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1. Neutrophilic leukocytosis a. Absolute neutrophil count above 7000/μL b. Etiology

i. Infection (e.g., acute appendicitis) ii. Sterile inflammation with necrosis (e.g., acute myocardial infarction) iii. Drugs (e.g., corticosteroids)

c. Pathogenesis i. Increased bone marrow production or release of neutrophils ii. Decreased activation of neutrophil adhesion molecules

Less neutrophils adhere to endothelial cells

Examples-corticosteroids, catecholamines, lithium 2. Neutropenia

a. Absolute neutrophil count below 1500/μL b. Etiology

i. Aplastic anemia ii. Immune destruction

Example-systemic lupus erythematosus (SLE) iii. Septic shock

c. Pathogenesis i. Decreased production ii. Increased destruction (e.g., complement, macrophages) iii. Activation of neutrophil adhesion molecules (e.g., endotoxins)

Increase the number of neutrophils adhering to endothelium

Disorders involving neutrophils page 228

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1. Neutrophilic leukocytosis a. Absolute neutrophil count above 7000/μL b. Etiology

i. Infection (e.g., acute appendicitis) ii. Sterile inflammation with necrosis (e.g., acute myocardial infarction) iii. Drugs (e.g., corticosteroids)

c. Pathogenesis i. Increased bone marrow production or release of neutrophils ii. Decreased activation of neutrophil adhesion molecules

Less neutrophils adhere to endothelial cells Examples-corticosteroids, catecholamines, lithium

2. Neutropenia a. Absolute neutrophil count below 1500/μL b. Etiology

i. Aplastic anemia ii. Immune destruction

Example-systemic lupus erythematosus (SLE) iii. Septic shock

c. Pathogenesis i. Decreased production ii. Increased destruction (e.g., complement, macrophages) iii. Activation of neutrophil adhesion molecules (e.g., endotoxins)

Increase the number of neutrophils adhering to endothelium

Disorders involving eosinophils

1. Eosinophilia a. Absolute eosinophil count over 700/μL b. Etiology

i. Type I hypersensitivity reaction Examples-bronchial asthma, reaction to penicillin, hay fever

ii. Invasive helminthic infection Examples-strongyloidiasis, hookworm infection Pinworms and adult ascariasis do not have eosinophilia (noninvasive).

iii. Polyarteritis nodosa, Addison's disease (cortisol deficiency) c. Pathogenesis

i. Release of eosinophil chemotactic factor from mast cells (e.g., type I hypersensitivity)

ii. No sequestering of eosinophils in lymph nodes (e.g., hypocortisolism) 2. Eosinopenia

a. Hypercortisolism (e.g., Cushing syndrome, corticosteroids)

b. Corticosteroids sequester eosinophils in lymph nodes.

Disorders involving basophils; basophilia

1. Absolute basophil count over 110/μL 2. Etiology

o Chronic myeloproliferative disorders (e.g., polycythemia vera)

Disorders involving lymphocytes

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1. Lymphocytosis a. Absolute lymphocyte count over 4000/μL in adults or over 8000/μL in children b. Etiology

i. Viral (e.g., mononucleosis) or bacterial (e.g., whooping cough) ii. Drugs (e.g., phenytoin) iii. Graves' disease

c. Pathogenesis i. Increased production ii. Decreased entry into lymph nodes

Example-lymphocytosis-promoting factor produced by Bordetella pertussis

2. Atypical lymphocytosis a. Etiology

i. Infection Examples-mononucleosis, viral hepatitis, cytomegalovirus infection,

toxoplasmosis ii. Drugs (e.g., phenytoin)

b. Pathogenesis i. Antigenically stimulated lymphocytes ii. Prominent nucleoli and abundant blue cytoplasm

3. Infectious mononucleosis a. Caused by Epstein-Barr virus (EBV) b. Pathogenesis

i. Primarily transmitted by kissing EBV initially replicates in the salivary glands and then disseminates.

ii. EBV attaches to CD21 receptors on B cells. Causes B-cell proliferation and increased synthesis of antibodies

iii. Virus remains dormant in B cells. Recurrences may occur.

c. Clinical findings i. Fatigue, tonsillitis ii. Hepatosplenomegaly, generalized lymphadenopathy

Danger of splenic rupture in contact sports iii. Rash develops if treated with ampicillin.

d. Laboratory findings i. Atypical lymphocytosis

Usually more than 20% of the total WBC count Atypical lymphocytes are antigenically stimulated T cells

ii. Positive heterophil antibody test Detects IgM antibodies against horse (most common), sheep, and bovine

RBCs iii. Positive antiviral capsid antigen test

Most sensitive test iv. Increased serum transaminases from hepatitis

Jaundice is rare. 4. Lymphopenia

a. Absolute lymphocyte count below 1500/μL in adults or below 3000/μL in children b. Etiology

i. Human immunodeficiency virus (HIV) ii. Immunodeficiency

DiGeorge syndrome (T-cell deficiency) Severe combined immunodeficiency (B- and T-cell deficiency)

iii. Immune destruction (e.g., SLE) iv. Corticosteroids v. Radiation

Lymphocytes are the most sensitive cells to destruction by radiation. c. Pathogenesis

i. Increased destruction Examples-lysis of CD4 helper T cells by the virus; apoptosis by

corticosteroids; immune destruction ii. Decreased production

Example-radiation iii. Decreased release from lymph nodes

Example-corticosteroids

Disorders involving monocytes; monocytosis page 231

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1. Absolute monocyte count over 800/μL 2. Etiology

a. Chronic infection (e.g., tuberculosis) b. Autoimmune disease (e.g., rheumatoid arthritis) c. Malignancy (e.g., carcinoma, malignant lymphoma)

3. Pathogenesis

o Response to chronic inflammation or malignancy

Leukemias (Acute and Chronic)

Epidemiology

1. Malignant diseases of bone marrow stem cells that may involve all cell lines 2. Risk factors

a. Chromosomal abnormalities Examples-Down syndrome, chromosome instability syndromes

b. Ionizing radiation c. Chemicals (e.g., benzene) d. Alkylating agents (particularly busulfan)

3. Age ranges for common leukemias a. Newborn to 14 years old

Acute lymphoblastic leukemia (ALL) b. Persons 15 to 39 years old

Acute myelogenous leukemia (AML) c. Persons 40 to 60 years old

.i AML (>60% of cases)

.ii Chronic myelogenous leukemia (∼40% of cases) b. Persons over 60 years of age

Chronic lymphocytic leukemia (CLL)

Epidemiology

1. Malignant diseases of bone marrow stem cells that may involve all cell lines 2. Risk factors

a. Chromosomal abnormalities Examples-Down syndrome, chromosome instability syndromes

b. Ionizing radiation c. Chemicals (e.g., benzene) d. Alkylating agents (particularly busulfan)

3. Age ranges for common leukemias a. Newborn to 14 years old

Acute lymphoblastic leukemia (ALL) b. Persons 15 to 39 years old

Acute myelogenous leukemia (AML) c. Persons 40 to 60 years old

.i AML (>60% of cases)

.ii Chronic myelogenous leukemia (∼40% of cases) b. Persons over 60 years of age

Chronic lymphocytic leukemia (CLL)

Pathogenesis

1. Block in stem cell differentiation o Monoclonal proliferation of neoplastic leukocytes behind the block

2. Leukemic cells

a. Replace the bone marrow Replace normal hematopoietic cells

b. Enter the peripheral blood

c. Metastasize throughout the body

Clinical findings in acute leukemia

1. Abrupt onset of signs and symptoms 2. Fever (infection), bleeding (thrombocytopenia), fatigue (anemia) 3. Metastatic disease

a. Hepatosplenomegaly b. Generalized lymphadenopathy c. Central nervous system (CNS) involvement (especially in ALL) d. Skin involvement (especially T-cell leukemias)

4. Bone pain and tenderness

o Due to bone marrow expansion by leukemic cells

Laboratory findings in acute leukemia page 232

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1. Peripheral WBC count a. Below 10,000/μL (normal) to more than 100,000/μL b. Blast cells usually more than 20% (e.g., myeloblasts, lymphoblasts).

2. Normocytic to macrocytic anemia

o Macrocytic if folate is depleted in production of leukemic cells 2. Thrombocytopenia (usually <100,000/μL) 3. Bone marrow findings

o Hypercellular with more than 20% blasts (e.g., myeloblasts, lymphoblasts)

Clinical findings in chronic leukemia

a. Insidious onset

b. Hepatosplenomegaly and generalized lymphadenopathy

Laboratory findings in chronic leukemia

a. Peripheral WBC count i. Similar to that of acute leukemia ii. Blast cells usually less than 10% iii. Evidence of maturation of cells

b. Normocytic to macrocytic anemia

o Macrocytic if folate is depleted in production of leukemic cells b. Thrombocytopenia (usually <100,000/μL)

o Exception in CML, in which thrombocytosis occurs in 40% of cases c. Bone marrow findings

o Hypercellular with less than 10% blasts

eoplastic Myeloid Disorders

Overview

1. Myeloid disorders are neoplastic stem cell disorders. o May involve one or more stem cell lines

2. Classification

a. Chronic myeloproliferative disorders b. Myelodysplastic syndrome

c. Acute myeloblastic leukemia

Overview

1. Myeloid disorders are neoplastic stem cell disorders. o May involve one or more stem cell lines

2. Classification

a. Chronic myeloproliferative disorders b. Myelodysplastic syndrome

c. Acute myeloblastic leukemia

Chronic myeloproliferative disorders

Table 12-1. Laboratory Findings in Polycythemias

PolycythemiaRBC Mass

Plasma Volume SaO2 EPO

Polycythemia vera ↑ ↑ Normal

↓

Appropriate polycythemia (e.g., COPD, cyanotic congenital heart disease)

↑ Normal ↓ ↑

Inappropriate polycythemia: ectopic EPO (e.g., renal disease) ↑ Normal Norma ↑

l

Relative polycythemia (e.g., volume depletion) Normal ↓ Normal

Normal

COPD, chronic obstructive pulmonary disease; EPO, erythropoietin; SaO2, oxygen saturation.

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1. Classification a. Polycythemia vera b. Chronic myelogenous leukemia c. Myeloid metaplasia with myelofibrosis d. Essential thrombocythemia

2. General characteristics a. Splenomegaly b. Propensity for reactive bone marrow fibrosis ("spent phase") c. Propensity for transformation to acute leukemia

3. Polycythemia a. Increased hemoglobin (Hb), hematocrit (Hct), and RBC count b. Plasma volume (PV) varies with the type of polycythemia. c. RBC count versus RBC mass

i. RBC count is the number of RBCs per μL of blood. ii. RBC mass is the total number of RBCs in the body in mL/kg. iii. RBC count is the ratio of RBC mass to plasma volume (PV).

shows the normal relationship between RBC count, RBC mass, PV, erythropoietin (EPO), and O2 saturation (Sao2).

d. Relative polycythemia i. Increased RBC count due to a decrease in PV

Example-volume depletion from sweating ii. RBC mass is normal.

No increase in bone marrow production of RBCs iii. Erythropoietin (EPO) and Sao2 are normal.

e. Absolute polycythemia i. Increase in bone marrow production of RBCs

Increased RBC count and RBC mass ii. Appropriate absolute polycythemia if there is a hypoxic stimulus for EPO release

Examples-primary lung disease, cyanotic congenital heart disease, living at high altitude

Decreased O2 saturation (Sao2) Increased RBC count, RBC mass, EPO Normal PV

iii. Inappropriate absolute polycythemia if there is no hypoxic stimulus for EPO release

Polycythemia vera (see below) Ectopic secretion of EPO (e.g., renal cell carcinoma)

Increased RBC count, RBC mass, EPO; normal PV and Sao2 4. Polycythemia vera

a. Pathogenesis i. Clonal expansion of the trilineage myeloid stem cell ii. Increase in RBCs, granulocytes (neutrophils, eosinophils, basophils), mast cells,

and platelets b. Clinical findings

i. Splenomegaly

ii. Thrombotic events due to hyperviscosity (e.g., hepatic vein thrombosis) iii. Signs of increased histamine (released from mast cells in the skin)

Ruddy face Pruritus after bathing Peptic ulcer disease (histamine stimulates production of gastric acid)

iv. Gout Due to increased breakdown of nucleated cells with release of purines

(converted to uric acid) c. Laboratory findings in polycythemia vera

i. Increased RBC mass and PV Only type of polycythemia with an increase in PV

ii. Absolute leukocytosis (leukocytes >12,000/μL) iii. Thrombocytosis (platelets >400,000/μL) iv. Decreased EPO

Increased O2 content inhibits EPO release. Only type of polycythemia with decreased EPO

v. Normal Sao2 vi. Hypercellular bone marrow with fibrosis in later stages

d. Summary table of the polycythemias 5. Chronic myelogenous leukemia (CML)

a. Epidemiology i. Usually occurs between 40 and 60 years of age ii. Risk factors

Exposure to ionizing radiation and benzene b. Pathogenesis

i. Neoplastic clonal expansion of the pluripotential stem cell This stem cell has the capacity to differentiate into a lymphoid or

trilineage myeloid stem cell. ii. t9;22 translocation of ABL proto-oncogene

Proto-oncogene fuses with the break cluster region (BCR) on chromosome 22 (BCR-ABL fusion gene).

c. Clinical findings i. Hepatosplenomegaly and generalized lymphadenopathy

Due to metastasis ii. Blast crisis

Usually occurs in ∼5 years Increase in numbers of myeloblasts or lymphoblasts Myeloblasts do not contain Auer rods (see below)

d. Laboratory findings i. Peripheral WBC count 50,000 to 200,000 cells/μL

Myeloid series in all stages of development ii. Normocytic to macrocytic anemia

Macrocytic if folate is depleted in the production of leukemic cells. iii. Platelet count

Thrombocytosis (40-50%), thrombocytopenia in the remainder of cases iv. Bone marrow findings

Myeloblasts less than 10% Hypercellular

v. Positive Philadelphia chromosome (95% of cases) It is not specific for CML and is present in other leukemias. It is not lost during therapy unless α-interferon is used.

vi. BCR-ABL fusion gene (100% of cases) Fusion gene is the most sensitive and specific test for CML

vii. Decreased leukocyte alkaline phosphatase (LAP) LAP is absent in neoplastic granulocytes and present in benign

granulocytes. 6. Myelofibrosis and myeloid metaplasia

a. Pathogenesis i. Marrow fibrosis occurs earlier than in other types of myeloproliferative disease. ii. Neoplastic cells are produced in the spleen and other sites (extramedullary

hematopoiesis, EMH). b. Clinical findings

i. Massive splenomegaly with portal hypertension ii. Splenic infarcts with left-sided pleural effusions

c. Laboratory findings i. Bone marrow fibrosis due to stimulation of fibroblasts ii. Peripheral WBC count 10,000 to 50,000 cells/μL iii. Normocytic anemia

Tear-drop cells (damaged RBCs) Leukoerythroblastic reaction

iv. Platelet count is variable (increased or decreased). 7. Essential thrombocythemia

a. Pathogenesis i. Neoplastic stem cell disorder with proliferation of megakaryocytes ii. Platelets are increased; however, they are nonfunctional.

b. Clinical findings i. Bleeding (usually gastrointestinal with concomitant iron deficiency) ii. Splenomegaly

c. Laboratory findings i. Thrombocytosis (platelets >600,000/μL)

Platelet morphology is abnormal. ii. Mild neutrophilic leukocytosis

iii. Hypercellular bone marrow with abnormal megakaryocytes

Myelodysplastic syndrome page 237

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1. Epidemiology o Usually occurs in men between 50 and 80 years old

2. Pathogenesis

a. Group of neoplastic stem cell disorders Chromosomal abnormalities in 50% of cases (e.g., 5q-, trisomy 8)

b. Frequently progresses to acute myelogenous leukemia (AML; 30% of cases) "Preleukemia"

2. Laboratory findings a. Severe pancytopenia

.i Normocytic to macrocytic anemia Dimorphic RBC population (microcytic and macrocytic)

.ii Leukoerythroblastic reaction b. Bone marrow findings

.i Ringed sideroblasts (nucleated RBCs with excess iron)

.ii Myeloblasts less than 20% (if >20%, disease is progressing to AML)

Acute myelogenous leukemia

Table 12-2. French-American-British Classification of Acute Myelogenous Leukemia (AML)

Class CommentsM0: Minimally differentiated AML No Auer rods

M1: AML without differentiation: 20%

Rare Auer rods

M2: AML with maturation Most common type (30-40% of cases).Auer rods present15-59-year-old age bracket

M3: Acute promyelocytic Numerous Auer rodsDIC is invariably presentt(15;17) translocationAbnormal retinoic acid metabolism: high doses of vitamin A may induce remission by maturing cells

M4: Acute myelomonocytic Auer rods uncommon

M5: Acute monocytic No Auer rodsGum infiltration

M6: Acute erythroleukemia Bizarre, multinucleated erythroblastsMyeloblasts present

M7: Acute megakaryocytic Myelofibrosis in bone marrowIncreased incidence in Down syndrome in children <3 years old

DIC, disseminated intravascular coagulation.

1. Epidemiology a. Usually occurs between 15 and 59 years of age b. French-American-British (FAB) classification is used

2. Cytogenetic abnormalities are common.

o Example-t(15;17) in acute promyelocytic leukemia (M3) 2. Clinical findings

i. Disseminated intravascular coagulation (DIC) is common. Invariable in acute promyelocytic leukemia

ii. Gum infiltration is common in acute monocytic leukemia (M5). 2. Auer rods

i. Splinter-shaped to rod-shaped structures in the cytosol of myeloblasts Auer rods are fused azurophilic granules

ii. Only present in acute myelogenous leukemia (M2 and M3) They are not present in myeloblasts in chronic myelogenous leukemia.

Lymphoid Leukemias

Acute lymphoblastic leukemia (ALL)

1. Epidemiology a. Most common leukemia in children (newborn to 14 years of age) b. Subtypes

i. Early pre-B-cell ALL (80%) ii. Pre-B-, B-, and T-cell ALL

2. Pathogenesis

o Clonal lymphoid stem cell disease 2. Early pre-B-cell ALL

a. Positive marker studies for common ALL antigen (CALLA, CD10) b. Positive marker studies for terminal deoxynucleotidyl transferase (TdT) c. t(12;21) translocation offers a favorable prognosis. d. Greater than 90% achieve complete remission.

At least two thirds of patients can be considered cured. 2. T-cell ALL

o CD10 negative and TdT positive 2. Clinical findings

o Metastatic sites similar to those of AML o B-cell types

Commonly metastasize to the CNS and testicles o T-cell type

Presents as anterior mediastinal mass or acute leukemia 3. Laboratory findings

o Peripheral WBC count 10,000 to 100,000/μL Over 20% lymphoblasts in peripheral blood

o Normocytic anemia with thrombocytopenia o Bone marrow findings

Bone marrow often totally replaced by lymphoblasts

Acute lymphoblastic leukemia (ALL)

1. Epidemiology a. Most common leukemia in children (newborn to 14 years of age) b. Subtypes

i. Early pre-B-cell ALL (80%) ii. Pre-B-, B-, and T-cell ALL

2. Pathogenesis

o Clonal lymphoid stem cell disease

2. Early pre-B-cell ALL

a. Positive marker studies for common ALL antigen (CALLA, CD10) b. Positive marker studies for terminal deoxynucleotidyl transferase (TdT) c. t(12;21) translocation offers a favorable prognosis. d. Greater than 90% achieve complete remission.

At least two thirds of patients can be considered cured. 2. T-cell ALL

o CD10 negative and TdT positive 2. Clinical findings

o Metastatic sites similar to those of AML o B-cell types

Commonly metastasize to the CNS and testicles o T-cell type

Presents as anterior mediastinal mass or acute leukemia 3. Laboratory findings

o Peripheral WBC count 10,000 to 100,000/μL Over 20% lymphoblasts in peripheral blood

o Normocytic anemia with thrombocytopenia o Bone marrow findings

Bone marrow often totally replaced by lymphoblasts

Adult T-cell leukemia

1. Epidemiology a. Malignant leukemia associated with human T-cell leukemia virus (HTLV-1) b. May present as a malignant lymphoma

2. Pathogenesis a. Activation of TAX gene, which inhibits the TP53 suppressor gene b. Leads to monoclonal proliferation of neoplastic CD4 helper T cells

3. Clinical findings a. Hepatosplenomegaly and generalized lymphadenopathy b. Skin infiltration

Common finding in all T-cell malignancies c. Lytic bone lesions

.i Due to lymphoblast release of osteoclast-activating factor

.ii Associated with hypercalcemia 2. Laboratory findings

a. Peripheral WBC count 10,000 to 50,000/μL .i Over 20% lymphoblasts .ii Positive CD4 marker study .iii Negative for TdT

b. Normocytic anemia and thrombocytopenia c. Bone marrow findings

Replaced by CD4 lymphoblasts

Chronic lymphocytic leukemia (CLL)1. Epidemiology

a. Occurs in individuals over 60 years old b. Most common overall leukemia c. Most common cause of generalized lymphadenopathy in the same age bracket

2. Pathogenesis

o Neoplastic disorder of virgin B cells (B cells that cannot differentiate into plasma cells) 2. Clinical findings

a. Generalized lymphadenopathy b. Metastatic sites similar to those of AML c. Increased incidence of immune hemolytic anemia

Both warm (IgG) and cold (IgM) types

3. Laboratory findings

d. Peripheral WBC count 15,000 to 200,000/μL

.i Lymphoblasts less than 10%

.ii Neutropenia

.iii Numerous "smudge" cells (fragile leukemic cells)b. Normocytic anemia (50% of cases) and thrombocytopenia (40% of cases) c. Bone marrow findings: usually replaced by neoplastic B cells d. Hypogammaglobulinemia is common.

Hairy cell leukemia

1. Type of B-cell leukemia o Most common in middle-aged men

2. Clinical findings

a. Splenomegaly (90% of cases) b. Absence of lymphadenopathy

Only leukemia without lymphadenopathy c. Hepatomegaly (20% of cases) d. Autoimmune vasculitis and arthritis

2. Laboratory findings a. Pancytopenia

Leukemic cells have hair-like projections

b. Positive tartrate-resistant acid phosphatase stain (TRAP)

Summary table of the lymphoid leukemias

Table 12-3. Summary of Acute and Chronic Lymphoid Leukemias

Leukemia DescriptionAcute lymphoblastic Most common leukemia in children

(Early pre-B type) Newborn to 14 years oldCALLA (CD10) and TdT positivet(12;21) offers a good prognosis

Chronic lymphocytic Virgin B cell leukemiaPatients > 60 years oldMost common cause of generalized lymphadenopathy in same age bracketHypogammaglobulinemia

Adult T cell HTLV-1 associationLeukemic cells CD4 positive and TdT negativeSkin infiltrationLytic bone lesions with hypercalcemia

Hairy cell B cell leukemiaCytoplasmic projectionsTRAP stain positiveSplenomegalyAbsence of lymphadenopathyPancytopeniaDramatic response to purine nucleosides

CALLA, common acute lymphoblastic leukemia antigen; HTLV, human T-cell leukemia; TdT, terminal deoxynucleotidyl transferase; TRAP, tartrate resistant acid phosphatase.

12 white blood cell disorders

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