White Cell Disorders Overview

Question 1

What are the three major clues you can bet from a bone marrow biopsy to determine a WBC disorder ?

Answer 1

1. What the abnormal cells look like 2. The immunophenytype of the abnormal cells 3. The Genotype of the abnormal cells.

Question 2

What are the normal contents of a core marrow biopsy ?

Answer 2

Erythroid, Myeloid, and Magakaryocytes.

Question 3

Is there iron in the bone marrow ?

Answer 3

Yes, on a histiocytic biopsy there will be ferritin in the stain.

Question 4

What are the 5 tumor markers for B cells

Answer 4

CD-45 CD-79 CD-20 IgG Kappa IgG Lambda

Question 5

What are the 5 common tumor markers for T cells ?

Answer 5

CD-45 TcR (CD-3) CD-7 CD-4 CD-8 (For the most part below ten)

Question 6

What is the process for immunophenotyping WBC’s ?

Answer 6

The same as with RBC’s except you have to lyse the RBC’s first.

Question 7

If a patient presents with a low white count, anemia, and thrombocytopenia what is this commonly called ?

Answer 7

Pancytopenia

Question 8

What do the different regions on this flow cytometry readout correspond to ?

Answer 8

Question 9

What does this region on the flow cytometry chart correspond to ?

Answer 9

This region is blasts

Question 10

How do you know what protein cells in the blood are expressing ?

Answer 10

Immunophenotyping

Question 11

What do you think this stain means ?

Answer 11

Question 12

What is the difference between normal staining and immunostaining ?

Answer 12

The immunostain has an antibody that will bind to a specific tumor marker displayed on the surface of the WBC

Question 13

Philedelphia Chromosome

Answer 13

Chronic Mylogenous Leukemia from a 9:22 translocation which most commonly shows up on FISH or traditional cytogenic examination.

Question 14

IF Cytogenetic and Fish turn up normal and you still suspect the patient has CML what test should you perform next ?

Answer 14

PCR based DNA and RNA sequencing can turn up a NPM-1 mutation

Complete genome sequencing from two different samples, one from the leukemia cells and one from the skin biopsy

Question 15

How many point mutations can lead to AML ?

Answer 15

720: 12 in the coding regions and up to 52 in the noncoding regions. You must always ask yourself if this is relevant to the pathogenesis or an independent mutation

**This is inefficent because typically only 4 are found in clinically significant cases.

Question 16

What are the 4 lineages that can cause malignancies in the marrow ?

Answer 16

1. Niave Lymphocytes
2. Megakaryocytes
3. Erythroid Lineage
4. Myleoid Lineage

Question 17

What causes acute leukemia ?

Answer 17

Rapidly proliferating bone marrow stem cells which will be indicated by blasts in the peripheral blood and bone marrow

Question 18

What caues myeloproliferative disease ?

Answer 18

Chronically proliferating clones which differentiate into terminally circulating blood cells

Question 19

What causes myelodysplastic syndromes ?

Answer 19

Poorly functioning clones

Question 20

If you have a mutation in the Myeloid lineage that causes Myeloid clones to proliferate indefinetly what is this called ?

Answer 20

Acute Myeloid Leukemia

Question 21

What will rapidly proliferating lymphoblastic clones in the peripheral blood indicate ?

Answer 21

Acute Lymphoblastic Leukemia

Question 22

What will rapidly proliferating hematopoietic stem cells in the marrow indicate ?

Answer 22

Acute Undifferentiated leukemia of mixed phenotypes

Question 23

Should you ever see blasts outside the bone marrow ?

Answer 23

No, Never this will indicate Lymphoblastic Lymphoma or Myleoid Sarcoma

Question 24

What should you think if you see proliferating blasts in the marrow and in the peripheral cells ?

Answer 24

Marrow blast number over 20 % in the marrow will indicate acute leukemia

Question 25

What is the blast immunophenotype ?

Answer 25

CD 34 +

Question 26

What is the myleoid blast phenotype ?

Answer 26

CD 34+ / CD 33+

Question 27

What is the immunophenotype of lymphoid blasts ?

Answer 27

CD 19+ / CD 10+

Question 28

Can leukemias be diagnosed with immunophenotypes alone ?

Answer 28

No because often the cancer will express mixed immunophenotypes but is a usefull tool.

Question 29

Blasts in Marrow and Blood Stream t(15;17) (q22;q12)

Answer 29

PML-RARA AML Subtype

Question 30

Blasts in Marrow and Blood Stream t(8;21) (q22;q22)

Answer 30

RUN X1-RUNXT1 AML Subtype

Question 31

Blasts in Marrow and Blood Stream t( 12;21) (p13, q22)

Answer 31

TEL-AML-1 ALL

Question 32

Blasts in Marrow and Blood Stream Cytogenetic testing negative

Answer 32

FLT3 Mutation (+) AML Subtype

Question 33

When you see blasts in the marrow and blood steram what should you do ?

Answer 33

What is the blast count ? What is the blast morphology ? What is the immunophenotype of the blast ? What is the genetic makeup of the blast ?

Question 34

In AML what are the two classes of translocations and mutations ?

Answer 34

Class 1 provide a proliferative and Survival advantage Class 2 provide impaired differentiation and apoptosis

Question 35

What are the class 1 Mutation Translocations ?

Answer 35

FLT3-ITD FLT3-TKD KIT RAS PTPN-11 JAK-2

Question 36

What are the class 2 mutation translocations ?

Answer 36

PML-RARA Runx1-Run1x1t1 CBFB-Myh11 MLL Fusions CEBPA NPM-1

Question 37

What is the Gilland Hypothesis for AML ?

Answer 37

It takes two classes of mutations or translocations to get AML

Question 38

What is the arrow pointing to ?

Answer 38

An Aeur Rod, This is a classical smear for Acute Myleoid Leukemia with an t(8;21) (q22, a22) Run X1- Run1X1 The smear shows myelocytes with some maturation with crystalization of the granule contents forming Auer Rods \*\*Remember these require a class 1 and a class 2 mutation

Question 39

Describe the morphology you see in this stain ?

Answer 39

This stain repersents Big Blasts, some of which can be cleaved to show bat wing blasts, with Many cytoplasmic granules and Auer rods in the sacs.

Question 40

What does CD-34 Cd-17 indicate on a immunophenotype ?

Answer 40

Blasts

Question 41

CD-13 CD-33 +

Answer 41

Granulocytes

Question 42

CD14 CD11b ?

Answer 42

Monocytes

Question 43

You hace blasts, monocytes, and Granulocytes in the peripheral smear, what kind of Leukemia is this ? Notice the eosinophilia

Answer 43

Acute Myeloid Leukemia

Question 44

What do you see on this peripheral smear ?

Answer 44

The morphology of these cells is Granulocytic, or Monocytic or Monoblastic

Question 45

NPM-1+ CEBPA+ But The Cytogenetic Testing Comes Back Normal

Answer 45

Acute Myleoid Leukemia

Question 46

t(15;17) q22,12

Answer 46

PML RARA AML subtype

Question 47

t(8;21) (q22,q22)

Answer 47

RUNx1-RUNTX1 AML subtype

Question 48

t(12;21) (p13,q22)

Answer 48

TEL AML -1 ALL Subtype

Question 49

What is the Gilliand Hypothesis

Answer 49

It requires two mutations for a neoplastic conversion into AML AML AML AML

Question 50

How would you detect PML-RARA RunX1- RunX1T1 CBFP-MYH11 MLL Fusions ?

Answer 50

These all are detected by Cytogenetic analysis

Question 51

t(8;21) with (q22, a22) CD34+ HLA-Dr+ CD13+ CD 33 weak

Answer 51

There are auer rods, that combined with the cell markers CD34 CD 13 HLA-Dr indicate this is Acute Myleoid Leukemia Auer Rods AML

Question 52

What are the B stem cell markers ?

Answer 52

CD-34 and TdT

Question 53

What are the lymphoid precursor markers in B cell development ?

Answer 53

CD-19 and CD-10

Question 54

What are the Pre-B cell markers ?

Answer 54

Cyto u and CD-20

Question 55

What transcription factors regulate progression from Stem Cells to Lymphoid Precursors ?

Answer 55

Question 56

Patient is presenting with DIC, Thrombocytopenia CD 33+ CD 13+ t(15;17)

Answer 56

In the blood we see big blasts with cytoplasmic granules in the neutrophils and auer rods. The t(15;17) will indicate a PML-RARA (Retinoic Acid Receptor) Prognosis Good Acute Myleoid Leukemia

Question 57

What transcription factor regulates transmission from PreB1 to PreB2

Answer 57

Question 58

Can Lymphoid Markers ever express myleoid markers ?

Answer 58

Yes they can express CD 13 and CD33

Question 59

t(9;22) (q34; q11.2)

Answer 59

BCR-ABL 1

Question 60

t(v;11q23)

Answer 60

MLL rearranged

Question 61

t(12;21) (p13, q22)

Answer 61

TEL AML-1 ETV6 RUNX1

Question 62

t(5;14) (q31, q32)

Answer 62

IL-3 IgH

Question 63

In leukemia what is the difference between Hyperdiploid and Hypodiploid

Answer 63

Hyperdiploid has over 5-0 chromosomes in the tumor and better prognosis

Question 64

t(9;22) (q34, q11.2) CD10+ CD19+ TdT+

Answer 64

The smear shows large agranular blasts CD10, CD19, TdT show you that is its Lymphoid This is Acute Lymphocytic Leukemia BCR-ABL prognosis is very poor for Leukemia

Question 65

What two cancers is the BCR-ABL mutation present in ?

Answer 65

ALL and CML

Question 66

IFKZ mutation is mutated in 84 percent of what type of cancer ?

Answer 66

Acute Lymphocytic Leukemia

Question 67

t(v;11q23) What will this mutation do ?

Answer 67

This mutation will lead to ALL, MLL, and AML. it fuses a transcription regulator

Question 68

What does the t(12;21) (p13, q22) transmutation do ?

Answer 68

TEL-AML-1 (ETV-6 RUNX-1) Usually associated with ALL. This is the ALL that has a 90% cure rate.

Question 69

t(14 q11; 10q24) with TdT+, CD3+, CD5+, Myleoid or B cell antigens

Answer 69

T-ALL most have a very poor prognosis Most have a translocation of a oncogene to a TCR promoter. This is a common motif for Lymphoid oncogenesis

Question 70

What are myeloproliferative diseases ?

Answer 70

A disease characterized by chronically proliferating clones which differentiate into circulating blood cells.

Question 71

What disease is characterized by all stages of granulocyte maturation present in the blood smear ?

Answer 71

Chronic Mylogenous Leukemia

Question 72

What disease is characterized by monocytes, promonocytes, and weird hybrids between monocytes and granulocytes ?

Answer 72

Chronic Myelomonocytic Leukemia

Question 73

What diseases are characterized by elevated RBC counts ? Elevated Platelet counts?

Answer 73

Polycytemia Vera Essential Thrombocytopenia or primary myelofibrosis

Question 74

How can you distinguish between Myeloproliferative disease and sepsis ?

Answer 74

Myeloproliferative diseases have the myleoid buldge and sepsis does not

Question 75

Answer 75

There is more Metas than myelocytes so this is a case of Sepsis

Question 76

What is this a case of ?

Answer 76

More Myelocytes than metas is Myeloproliferative disease

Question 77

Answer 77

This is CML and the peripheral smear shows Granulocyte precursors

Question 78

What is mastocytosis ?

Answer 78

Mast cells similiar to basophils but longer lived and non circulating

Question 79

How do mast cell neoplasms normally present ? What is the most common site of mast cell neoplasms ?

Answer 79

As cutaneous lesions in kids, Uticaria Pigmentosum The bond marrow but often other organs can be involved

Question 80

This immunophenotype is positive for Tryptase , CD 117, CD25 What kind of mutation will be likely with this presentation

Answer 80

Mastocytosis, notice the aggregates of band looking cells with round spindel shaped, and sometimes containing eosinophillia. cKIT is common in this presentation

Question 81

What type of mutation is present in Polycytemia Rubivera ? What do these patients present with ?

Answer 81

Jak-2 Mutations are present in over 95 precent Thrombosis, Hypertension Stroke and MI

Question 82

Increased RBC's ? Increased Platelets ? Increased Platelets ?

Answer 82

Polycytemia Vera Essential Thrombocytemia Primary Myelofibrosis

Question 83

The patient is presenting with thrombosis, hypertension and stroke with a Jak-2 Mutation

Answer 83

Polycytemia Vera

Question 84

What do you see in this smear ?

Answer 84

A greatly increased number of platelets and Megakaryocytes This is essential thrombocytopenia

Question 85

What can you see in this peripheral smear ?

Answer 85

Increased Megakaryocytes bizarre shapes and clustering Fibrosis. This is Primary Myelofibrosis

Question 86

What can myelodysplastic syndrome progress to ?

Answer 86

Acute Leukemia

Question 87

When you see unexplained pancytopenia and this on the peripheral smear, what will you suspect ?

Answer 87

Refractory Cytopenia It can also present with ringed cyteroblasts

Question 88

What kind of cell is this ? With a 5q deletion what disease will this cause ?

Answer 88

Mononuclear Megakaryocyte MDS

Question 89

What is the abnormal spear associated with ?

Answer 89

Refractory Cytopenia