4- Introduction to WBC Disorders Reactive an Neoplastic Myeloid Processes Targeted Leukemia Therapy

Question 1

In order to make a diagnosis of acute leukemia, how many blasts (at a minimum) would you have to se in a peripheral blood (or bone marrow) smear?

Answer 1

over 20%

Question 2

What cells are these?

Answer 2

Neutrophils! You rock!

Question 3

What type of WBC would be elevated with a streptococcal tonsilitis infection? How about Mono? Whooping cough? Cutaneous larva migrans? G-CSF administration?

Answer 3

mono- lymphocytes

strep tonsilitis- neutrophils

whooping cough- lymphocytes

cutaneous larva migrans- eosinophils

G-CSF- neutrophils (but not as elevated as with a bacterial infection)

Question 4

What would the following laboratory tests be used to confirm?

JAK2 mutational analysis

Throat culture

Monospot test

Cytogenetics for the philadelphia chromosome

flow cytometry for Tdt(+) cells

Answer 4

JAK2 mutational analysis- PV, ET, PMF

Throat culture: Strep tonsilitis (neutrocytoses)

Monospot test: Infectious mononucleosis

Cytogenetics for the philadelphia chromosome: CML

flow cytometry for Tdt(+) cells: ALL (notice this is not the word all, I was confused at first haha)

Question 5

What is the significance of “toxic changes” in peripheral blood neutrophils?

Answer 5

indicates the presence of primary granules

Question 6

What disease is associated with Disseminated Intravascular Coagulation (DIC) and has the following histology?

Answer 6

Acute Myeloid Leukemia

Question 7

Which cytogenic abnormality is associated with the following histology slide?

Answer 7

t(15;17)

There are a LOT of Auer rods so it is probably APL

Question 8

What is the funcional defect that is associated with the product of the PML-RARa fusion gene? Therefore what therapy is recommended?

Answer 8

A block in terminal differentiation due to retinoic acid receptor disruption

therapy is all trans retinoic acid

Question 9

Which cytogenic/molecular abnormalities have a similar prognostic significance to t(15;17), in a patient with AML?

Answer 9

t(8;21)

inv(16) aka t(16;16)

Question 10

Leukemias are about 5% of all cancers. (S/O to Miss Matter). WHat percentage of adult leukemias are Acute Myelogenous Leukemia? What percentage of their etiologies re therapy related?

Answer 10

AML is 30% of adult leukemias and 10% of them are due to therapy

Question 11

What 3 things does the prognosis of AML depend on?

Answer 11

Age

cytogenetics

Molecular

Question 12

What is the difference bewteen cytogenetics and Molecular?

Answer 12

Cytogenetics is BIG, like a peice of highway compeltely dropped off

MOlecular is SMALL, like a little pot hole in the road (usually point mutations)

Question 13

WHat does induction mean? And what drugs are usually used furing the induction process for AML?

Answer 13

Induction is inducing the patient into remission!

“7+3” with Ara-C + Daunorubicin

+Midostaurin (with FLT3 mutation)

Mylotarg (with CBF mutation) (immunotherapy)

Question 14

What is consolidation?

Answer 14

Consolidation is ensuring that the patient is in remission!

chemotherapy

or stem cell transplantation

Question 15

WHat does this patent likely have and why?

Answer 15

Chronic myelogenous leukemia

• blasts are <20% so not acute
• leukocytoses

Question 16

In MDS would you have leukocytoses or leukopenia?

Answer 16

Leukopenia

Question 17

Hypercellular bone marrow with effective hematopoiesis is seen in what?

Answer 17

Myeloproliferative Neoplasms (PV, ET, PMF, CML)

Question 18

What are the basic questions you should ask yourself to assess what disease a person has, and then also to assess its severity?

Answer 18

• Are blasts>20%
  
  • if yes, its acute= emergency
    
    • AML or ALL
  • if no, chronic= not emergency
• What cells are elevated?

Question 19

WHat is hypercellular bone marrow with ineffective hematopoiesis associated with?

Answer 19

MDS

Question 20

What is Hypercellular bone mrrow with extensive fibrosis associated with?

Answer 20

PMF

Question 21

Leukocytes positive for CD10 is associated with what?

Answer 21

ALL

Question 22

Leukocytes positive for JAK2V617F mutation suggestive of?

Answer 22

MPN :PV, EET, PMF

Not CML bc that is tyrosine kinase

Question 23

What protein does the Philadelphia result in and what is the translocation?

Answer 23

The philadelphia chromosome, which brings about the BCR-ABL fusion protein is the consequence of t(9;22)

Question 24

WHat is the functional defect that is associated with the product of the BCR-ABL fusion gene? What therapy is often used?

Answer 24

A constitutively activated tyrsine kinase

A tyrosine kinase inhibitor is recommended for CML

Question 25

What is Chronic Myelogenous Leukemia (CML)? What are 2 hallmarks? Etiologies?

Answer 25

* Clonal myeloproliferative disorder of pluripotent stem cells. Increased proliferation and decreased apoptosis * Hallmarks: * Cytogenetic- Philidephia chromosome * Molecular-BCR/ABL * Etiology: Irradiation \<5%, Unkown 95%

Question 26

What are the 3 phases of CML progression without treatment?

Answer 26

Chronic Accelerated Blast phase without treatment people usually go through all the phases and die within 7 years

Question 27

How does a tyrosine kinase inhibitor work? When do we use it?

Answer 27

Typically ATP binds to BCR ABL A TKI blocks the ATP binding sit so ATP can't bind No proliferation, Cell dies \*\*Used for CML!

Question 28

What are 5 TKIs? How effective are these?

Answer 28

Imatinib Dasatinib Nilotinib Bosutinib Ponatinib The lifespan of people on this drug are about the same as a person without CML! Unfortunately the side effects are brutal so even though a person's survival is preserved, their quality of life is not

Question 29

A patient has elevated hemoglobin and platelets, and a JAK2 mutational analysis is homozygous for the V617F mutation. What lab finding is likely present?

Answer 29

Decreased EPO This patient probably has PV

Question 30

A patient has elevated hemoglobin and a spleen palpable 4cm at MCL presenting with fatigue, cachexia, bone pain, night sweats and the following histology. What lab test would be positive to confirm the diagnosis?

Answer 30

JAK2 mutational analysis. This is PMF!

Question 31

What are the 4 MPNs? What mutations typically cause them?

Answer 31

Polycythemia vera (JAK2) Essential thrombocythemia (JAK2) Primary myelofibrosis (JAK2) Chronic Myeologenois leukemia (Tyrosine kinase)

Question 32

A patient presents with pancytopenia, hyperceullar bone marrow, and frequent hypogranular and hypolobated neutrophils, and small, hypolobated megakaryocytes. What is the most likely diagnosis?

Answer 32

Myelodysplastic syndrome MDS- Pancytopenia (ineffective hematopeiesis) and hypercellular bone marrow

Question 33

What is the most important diagnostic criterion in differentiating myelodysplastic syndrome from and acute myeloid leukemia with myelodysplasia-associated changes?

Answer 33

Bone marrow blast percentage! in AML blast\>20%

Question 35

What cytogenic abnormality is most likely to be found in a patient with MDS? What is the most likely treatment?

Answer 35

Monosomy 7 ## Footnote **A hypomethylating agent**

Question 36

What are the therapies for myelodysplastic syndrome?

Answer 36

Stem cell transplantation (BM transplant) Supportive care +/- growth factors hypomethylating agents lenalidomide histone deacetylase inhibitors

Question 37

What is the Molecular mechanism for MDS? How do the therapies interfere with this?

Answer 37

Hypermethylation of genes silences them blocking gene expression leading to a differentiation problem (MDS) Hypomethylating agents work by preventing DNAmethytransferase from hypermethylating

Question 38

How do hypomethylating agents help with lifespan of patients with MDS?

Answer 38

9.4 months

Question 39

What are the 3 categories of leukemias? Which ones fall into each category?

Answer 39

* Problems with Differentiation * MDS * Problems with Proliferation * CML and /CLL * PV * ET * PMF * Problems with BOTH DIfferentiation and proliferation * AML and ALL