Acute Myeloid & Lymphoid Leukemias

Down syndrome

M7 Megakaryoblastic leukemia has an association with what chromosomal disease?

Acute myeloid leukemia

*Broad category* of acute leukemia commonly seen in adults (mean age = 60) that is positive for *auer rods, CD13, CD33, and CD 34; myeloperoxidase, and non-specific esterase*?

Cytarabine

*M4 (myelomonocytic) AML* that is due to *inversion of chromosome 16* has a GREAT prognosis when it is treated with what chemotherapeutic agent?

Hyperdiploid (too many chromosomes) 12;21 translocation (TEL/AML1 gene fusion)

2 Cytogenetic findings that indicate a GOOD prognosis for Precursor B Lymphoblastic Leukemia/Lymphoma?

M7: megakaryoblastic leukemia **Dry tap is due to malignant cels producing factors that promote fibrosis in the bone marrow. **CD13 and 33 = myeloid **cCD41 and cCD61 = Megakaryoblastic

A pt presents with *puffy, swollen, bloody gums*. You go to get a bone marrow sample, but get no cells (*dry tap*). Immunophenotype of blood cells reveals cells that are *cCD41, cCD61, CD13 and CD33 positive* what form of leukemia does this pt have?

M0 = Myeloid with minimal differentiation M1 = Myeloid without maturation M2 = Myeloid with maturation M3 = Promyelocytic M4 = Myelomonocytic M5 = Monoblastic and Monocytic M6 = Erythroid M7 = Megakaryoblastic **Top and bottom of the list: rare, do poorly, not associated w/ a classic genetic change **Middle of the list: more common, do better, have classic genetic changes

Acute Myeloid Leukemias: M0 = ? M1 = ? M2 = ? M3 = ? M4 = ? M5 = ? M6 = ? M7 = ?

M1: Myeloid without maturation

Aggressive acute myeloid leukemia that presents with bone marrow failure. Has >90% blasts (less than 10% maturing PMNs) and is CD13, CD33, CD34, and *myeloperoxidase* positive, with *auer rods* present on microscopy?

M5: monoblastic and monocytic AML **Blasts (including promonocytes) must be >20% and must have less than 20% neutrophils (PMNs)

Aggressive form of AML that often presents with *puffy, swollen, bleeding gums*. *Auer rods are absent*. The cells are CD13, CD33, *CD14, CD4, CD11, and CD36 positive*

Acute lymphoid leukemia **CD19 and CD22 = B cell **cCD3 and CD2 = T cell

Broad category of acute leukemia commonly seen in *children under 6*. That is TdT positive, CD19/CD22 positive, OR cCD3/CD2 positive?

Myeloid lineage (i.e. neutrophils) **If your markers have 3s in them, you are MYELOID

Cells with the markers: *CD13, CD33, and CD34* come from what lineage?

B cells **If your markers are around 20, you will become a B cell

Cells with the markers: *CD19, CD20, and CD22* will become what type of cells?

T cells (lymphoid lineage) **If your markers are single digit, you are LYMPHOID and will become a T cell*

Cells with the markers: *CD2, CD3, CD4, CD7, and CD8* will become what type of cells?

1. *All Trans-Retinoic Acid* 2. *Anthracycline*

EXAM Q: M3 (Promyelocytic leukemia) is due to a 15;17 translocation that fuses the RARα and PML genes. What two step treatment for this AML has a EXCELLENT response?

20%

EXAM Q: To be categorized as an acute myeloid leukemia, there must be greater than _____% Blasts in the blood or bone marrow.

1. Pt is Hyperdiploid (too many chromosomes) 2. Age 4-10 3. WBC count is low to normal 4. Pt initially responds to therapy

EXAM Q: What are 4 indicators of a GOOD pediatric prognosis for Precursor B Lymphoblastic Leukemia/Lymphoma?

M2 = 8;21 translocation AML1/ETO genes fuse

EXAM Q: What mutation is associated with M2 acute myeloid leukemia (myeloid with maturation)? What two genes are fused by this mutation?

M3 = 15;17 translocation PML/RARα genes fuse

EXAM Q: What mutation is associated with M3 acute myeloid leukemia (Promyelocytic)? What two genes are fused by this mutation?

M4 = Inversion of chromosome 16 CBF-β/ MYH11 fusion

EXAM Q: What mutation is associated with M4 acute myeloid leukemia (myelomonocytic)? What tow genes are fused by this mutation?

M5 = 9;11 translocation MLLT3/MLL genes fuse

EXAM Q: What mutation is associated with M5 acute myeloid leukemia (monoblastic and monocytic) What two genes are fused by this mutation?

M6a: erythroleukemia

Form of AML that presents as a *malignancy of RBCs* with *erythroblasts* present in the blood and *>20% of the non-erythroid cells being myeloblasts*?

Precursor T Lymphoblastic Leukemia/Lymphoma **Lymphoma presentation predominates!!! **15% of childhood acute lymphoid leukemias **25% of adult acute lymphoid leukemias

Form of Acute Lymphoid Leukemia/Lymphoma that typically presents as a mediastinal mass with thymic involvement?

Precursor B Lymphoblastic Leukemia/Lymphoma

Form of Acute Lymphoid Leukemia/Lymphoma that typically presents in *children under 18 years old* and most commonly has a *leukemoid presentation*?

Precursor B Lymphoblastic Leukemia/Lymphoma **TdT lets you know it is a blast **CD's around 20 = B cell

Form of Acute Lymphoid Leukemia/Lymphoma that typically presents with the following immunophenotype: - TdT - HLA-DR - CD19 - CD10 - CD22

M2: Myeloid with maturation **Cell origin = early PMN precursor **CD15 = marker of the secondary granules

Form of acute myeloid leukemia that presents with bone marrow failure and *> 10% mature PMNs, with less than 20% of them being monocytic*. Auer rods are present. The cells are CD13, CD33, and CD34 positive. In addition, the cells are *CD15 and myeloperoxidase positive*?

M5a: monoblastic M5b: monocytic

Form of the M5 phenotype where the affected cells are more immature? Form of the M5 phenotype where the affected cells are more mature?

M4: myelomonocytic **Cell origin = PMN-Monocyte Split Precursor **CD13, 33, and 34 = myeloblasts **CD14, 4, 11, and 36 = monoblasts

In this Acute Myeloid Leukemia, there are two groups of cells: *One group is CD13, CD33, and CD34 positive. The other group is CD14, CD4, CD11, and CD36 positive.* What AML is this?

M6a: erythroleukemia **CD13 and CD33 = myeloid **Glycophorin A and Heme A = RBCs

In this form of AML, one set of cells are *CD13 and CD33 positive* while another set of offending cells are *Glycophorin A and Heme A positive*?

M3 (Promyelocytic) → due to a 15;17 translocation M5 (monoblastic or monocytic) → due to a 9;11 translocation

In what two phenotypes of AML is *Disseminated Intravascular coagulation* common?

20%

Must have greater than ____% megakaryoblasts for the leukemia to be considered megakaryoblastic (M7)?

CNS Lymph nodes Spleen Liver Gonads Skin

Other than the thymus, what are some common tissues for Precursor T Lymphoblastic Leukemia/Lymphoma to present?

T cell receptor gamma, beta, or delta-alpha genes

Precursor T Lymphoblastic Leukemia/Lymphoma often presents with genetic translocations involving what gene?

Cytarabine

The 8;21 translocation form of M2 AML (myeloid with maturation) has a very good response to treatment with high long term survival when treated with what drug?

Precursor T Lymphoblastic Leukemia/Lymphoma **TdT = Blasts **Single digits = T cells **Prognosis is now the SAME as B cell Acute lymphoid leukemia

This acute lymphoid leukemia commonly presents with the following immunophenotype: - TdT - CD1a - CD2 - CD3 - CD4 - CD5 - CD7 - CD8

M3: Promyelocytic leukemia **Note the MASSIVE amounts of Auer rods in the cytoplasm **The lysis of these cells w/ release of Auer rods is largely responsible for the Diffuse Intravascular Coagulopathy seen in M3 AML

This cell will be seen in what type of Acute Myeloid Leukemia?

M3: Promeylocytic leukemia **RARα = Retinoic acid receptor (17) **PML = Promyelocytic leukemia gene (15)

This form of AML commonly presents with *Disseminated Intravascular Coagulopathy (DIC)*, and is ALWAYS due to a *15;17 translocation* that fuses the *RARα and PML genes*?

M3: Promyelocytic leukemia **Blasts & Promyelocytes > 20% **CD34 negative because CD34 is a marker of blasts and these cells are promyelocytes

This form of AML is CD33, CD13, and myeloperoxidase positive, but is *CD34 NEGATIVE*?

M4: Myelomonocytic Cell origin = PMN-Monocyte split precursor

This form of AML presents with marrow failure and has *>20% PMNs, with at least 20% of those being monocytic*? What is the cell origin for this AML?

M0 = myeloid with minimal differentiation **Very rare w/ poor outcome **Cell origin = myeloid stem cell

This form of acute myeloid leukemia presents with >20% blasts that demonstrate minimal maturation and *no Auer rods*. Phenotypic analysis shows CD13, CD33, and CD34. What acute myeloid leukemia is this?

*8;21 translocation:* fusion of AML1 & ETO **Typically seen in younger patients.

This translocation is the most common cytogenetic change in AML and creates the M2 morphology (myeloid with maturation)?

- 8:21 translocation - 15:17 translocation - Inversion on chromosome 16 **Can still be an acute myeloid leukemia even if there is less than 20% blasts in the blood or bone marrow

To normally be classified as an acute myeloid leukemia, There must be >20% blasts in the blood or bone marrow. What 3 specific cytogenetic abnormalities are exceptions to this rule?

9;22 translocation (BCR/ABL gene fusion) **This translocation is ALSO classically seen in chronic myelogenous leukemia Hypodiploid (too few chromosomes)

Two cytogenetic findings that indicate a POOR prognosis for Precursor B Lymphoblastic Leukemia/Lymphoma?

M5: monoblastic or monocytic M7: Megakaryoblastic

Two forms of AML that present with puffy, swollen, bloody gingiva?

M6b: erythroid leukemia **Must differentiate M6b (erythroid leukemia) from a B12/folate deficiency!!!

Very rare AML with a rapid and poor outcome where >80% of the cells are erythroid and there is NO myeloblast increase. Cells are Glycophorin A and Heme A positive.

*Auer rods:* cytoplasmic crystals of myeloperoxidase

What characteristic finding in this cell indicates that it comes from a myeloid lineage?

9;11 translocation **Disseminated intravascular coagulopathy is common!

What genetic mutation is often associated with M5 AML (monoblastic or monocytic) that *occurs in children*?

Monocyte precursor

What is the cell of origin of an M5 AML (monoblastic or monocytic)?

All trans-retinoic acid differentiates the cells into a more mature form with *less Auer rods*. **This prevents the diffuse intravascular coagulopathy that would be seen if this AML was just treated with chemotherapy. (high levels of Auer bodies cause DIC).

What is the function of all trans-retinoic acid when treating promyelocytic leukemia.

Inversion of chromosome 16 Core Binding Factor Beta & Smooth Muscle Myosin Heavy chain ***With this inversion, less than 20% of the cells can be blast, and you can still make the diagnosis of AML*

What is the most common genetic change found in M4 AMLs (myelomonocytic)? What two proteins fuse?

GREAT in pediatric populations (95% remission rate w/ 80% cure rate)

What is the prognosis for BOTH precursor B and T lymphoblastic Leukemia/Lymphomas?