Leukemias

Question 1

Blood Cell Lineages Chart

Answer 1

Question 2

Normal Bone Marrow Cellularity

Answer 2

• 100 minus the pts. age

Question 3

Causes of Leukemia Chart

Answer 3

Question 4

Causes of Leukemia

Answer 4

• Oncoproteins cause an arrest in maturation
• Mutations in transcription factors that give tumor cells a growth advantage
• Genetic diseases that promote genomic instability have greater likelihood of developing leukemia

Question 5

Leukemia

Answer 5

• CBC almost always abnormal
• Abnormalities in at least 2 major lineages
• Anemia usually normocytic, normochromic
• WBC elevated in >50% of cases due to circulating blasts
• 20% pts. will have WBC >100 x 10^9/L
• Rare cases are leukopenic

Question 6

Monoclonal Antibody Markers

Answer 6

• Major lymphoid markers: CD3 (T-cells), CD20 (B-cells)
• General blast marker: CD34
• Lymphoblast marker: TdT (terminal deoxytransferase)

Question 7

Acute vs. Chronic

Answer 7

• Acute refers to a process involving immature cells (notably blasts) i.e.:

*acute myeloid leukemia

*acute lymphoblastic leukemia

• Chronic refers to a process involving mature cells i.e.:

*chronic lymphocytic leukemia (B-cells)

*Note: chronic myelogenous leukemia is classified as a myeloproliferative neoplasm

Question 8

AML Epidemiology

Answer 8

• 70% of all acute leukemia
• Most cases seen in adults

Question 9

AML Clinical Presentation Chart

Answer 9

Question 10

Acute Myeloid Leukemia

Answer 10

• Defined as finding >20% myeloid blasts in bone marrow, although certain genetic findings define the diagnosis even w/ <20% blasts
• Auer rods; specific for blasts of myeloid lineages, most commonly seen in acute promyelocytic leukemia

Question 11

AML WHO Classification

Answer 11

• AML w/ recurrent chromosomal rearrangements

*t(8;21); CBFalpha/ETO fusion gene

*inv(16); CBFbeta/MYH11 fusion gene

*t(15;17); RARalpha/PML fusion gene (one of the most important ones to recognize b/c it can be deadly within a short amount of time)

*t(11a23;v); diverse MLL fusion genes

• Defines leukemia even if <20% blasts are present

Question 12

Acute Promyelocytic Leukemia (APML)

Answer 12

• t(15;17) PML-RARalpha disrupts terminal differentiation of granulocytes
• Toxic enzymes from Auer rods = disseminated intravascular coagulation
• Must treat w/ all-trans-retinoic acid (ATRA)

Question 13

Acute Megakaryocytic Leukemia

Answer 13

• Megakaryoblasts predominate
• Huge blasts w/ cytoplasmic blebs
• Can be seen in Down Syndrome

Question 14

Acute Lymphoblastic Leukemia (ALL)

Answer 14

• Cell of origin is usually B-cell precursor
• Less cytoplasm than AML, no Auer rods
• More dense chromatin, fewer nucleoli, usually lack cytoplasmic granules

Question 15

ALL Clinical Presentation

Answer 15

• Present more acutely
• Most common leukemia in children
• Symptoms of bone marrow suppression (low counts)

Question 16

Immunoprofile of ALL

Answer 16

• TdT+
• CD19+ early B-cell differentiation
• CD10+ (marker of early pre-B-cell differentiation aka CALLA)

Question 17

ALL Prognosis

Answer 17

Question 18

Chronic Leukemias

Answer 18

• B-cell chronic lymphocytic leukemias

*chronic lymphocytic leukemia (CLL)

*B-cell prolymphocytic leukemia (PLL)

*Hairy cell leukemia (HCL)

• T-cell chronic lymphoid leukemia

*T-cell prolymphocytic leukemia (T-PLL)

*T-cell large granular lymphocyte leukemia

*Adult T-cell leukemia/lymphoma (ATLL)

*Sezary syndrome

• Mature clonal disorders

*involved blood and bone marrow

*may infiltrate other organs ie.e lymph nodes and spleen

• Usually affect older adults
• Indolent, gnerally better prognosis

Question 19

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Answer 19

• Most common leukemia of adults
• May transform to diffuse large B-cel lymphoma (Richter transformation)
• Profound lymphocytosis

Question 20

CLL vs. Reactive Lymphocytosis

Answer 20

• Reactive lymphocytosis:

*infectious mononucleosis (EBV)

• Mature, non-reactive lymphocytosis:

*pertussis

Question 21

Richter Transformation

Answer 21

• Progression of CLL/SLL to diffuse large B-cell lymphoma

Question 22

Hairy Cell Leukemia

Answer 22

• Rare, B-cell leukemia- 2% of all lymphoid neoplasms
• Middle aged- elderly adults, indolent
• Tumor cells predominantly in bone marrow and spleen, may present w/ splenomegaly and pancytopenia
• Neoplastic cells w/ hair-like cytoplasmic projections
• Tartrate resistant acid phosphatase (TRAP), CD11c, CD25, CD103, and Annexin A1 are positive (specific markers expressed by these cells)

Question 23

T-cell Prolymphocytic Leukemia (T-PLL)

Answer 23

• Rare
• Average 70 y/o, men>women
• Presenting sx: splenomegaly, hepatomegaly, lymphadenopathy, skin lesions
• Prolymphocytes usually >90% of all lymphocytes
• Lymphocytes express CD3

Question 24

Adult T-cell Leukemia/Lymphoma

Answer 24

• Neoplasm of CD4+ T-cell infected by HTLV-1 (Human T-cell leukemia virus)
• Endemic in Japan and Caribbean
• Skin lesions, lymphadenopathy, peripheral blood lymphocytosis, hypercalcemia
• Clover leaf and flower cells

Question 25

Sezary Syndrome

Answer 25

- Leukemia form of mycosis fungoides, a mature T-cell lymphoma of CD4+ cells that presents in the skin