WBC disorders

Question 1

What is hairy cell leukemia?

Answer 1

A neoplastic proliferation of mature B cells characterized by hairy cytoplasmic processes

Question 2

How is hairy cell leukemia diagnosed?

Answer 2

These cells show hairy cytoplasmic processes on blood smear and are positive for tartrate-resistant acid phosphatase (TRAP) stain.

Question 3

What are the clinical features of hairy cell leukemia?

Answer 3

Everything can be summed up as TRAP:

• -the cells are TRAP positive
• -marrow fibrosis (the cells get “trapped” in the marrow–> pancytopenia)
• -(hepato)splenomeglay (accumulation of hairy cells in the red pulp of the spleen–they get “trapped”)
• -LAD is usually absent

Question 4

How do you treat hairy cell leukemia?

Answer 4

2-CDA (cladribine)

adenosine deaminase inhibitor; leads to toxic accumulation of adenosine in neoplastic B cells

Question 5

t(9;22)

Answer 5

the Philadelphia chromosome

CML (bcr-abl hybrid)

Question 6

t(8;14)

Answer 6

Burkitt lymphoma (c-myc activation)

14 = Fc heavy chain gene

Question 7

t(11;14)

Answer 7

Mantle cell lymphoma (cyclin D activation)

Question 8

t(14;18)

Answer 8

Follicular lymphomas (bcl-2 activation)

Question 9

t(15;17)

Answer 9

M3 type of AML (responsive to all-trans retinoic acid)

Question 10

Where does fetal hematopoiesis occur?

Answer 10

Yolk sac 3-8 weeks (3rd week)
Liver 6 weeks to birth (one month)
Spleen 10-28 weeks (2-4 months)
Bone marrow 18 weeks to adult (after 4 months)

Question 11

What units is fetal hemoglobin composed of? How does its affinity for oxygen compare to adult Hb and why?

Answer 11

Fetal hemoglobin consists of alpha2gamma2

It has a higher affinity for oxygen than HbA (adult Hb) due to less avid binding of 23BPG (recall: 2,3BPG shift the oxygen dissocation curve to the right, promoting oxygen unloading).

This allows fetal Hb to extract oxygen from maternal Hb across the placenta

Question 12

What are some basic principles of myeloproliferative disorders?

Answer 12

(1) These disorders are a neoplastic proliferation of mature cells of the myeloid linage
(2) diseases of late adulthood (avg. age is 50-60)
(3) sub-categorized based upon which myeloid cell is predominantly produced.
(4) result in hypercellular bone marrow, and increased WBC (due to an increase in the number of granulocytes)

Question 13

What are the complications of Myeloproliferative Disorders?

Answer 13

(1) Increased risk of hyperuricemia, sue to the high turnover of cells
(2) progession to marrow fibrosis
(3) transformation to Acute Leukemia

Question 14

What is chronic myeloid leukemia (CML)?

Answer 14

A neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors.

Question 15

What cell type is characteristically increased in CML?

Answer 15

Basophils

Question 16

What is the cause of CML?

Answer 16

t(9;22) translocation. (Philadelphia chromosome, bcr-abl fusion protein with increased tyrosine kinase activity)

Question 17

What is the first-line treatment of CML?

Answer 17

imatinib (gleevac)

Question 18

Clinical features of CML

Answer 18

Splenomegaly

enlarging spleen suggests the disease is getting worse, may herald the transformation to to acute leukemia (AML in 2/3 of the cases, ALL in 1/3)

Question 19

What is a leukemoid reaction?

Answer 19

It is a reactive neutrophilic leukocytosis

ie, an acute inflammatory response to an infection

Question 20

How can CML be distinguished from a leukemoid reaction?

Answer 20

(1) presence of t(9;22) – absent in leukemoid reaction
(2) Increased basophils – absent in leukemoid reaction
(3) Negative leukocyte alkaline phosphatase (LAP) stain –granulocytes in a leukemoid reaction are positive for LAP)

Question 21

What is polycythemia vera (PV)

Answer 21

A neoplastic proliferation of mature myeloid cells, particularly RBCs

Question 22

What mutation is PV classically associated with?

Answer 22

JAK2 kinase mutation