Acute myeloid leukemia

Содержание

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PLAN Introduction Pathogenesis Classification Types Conclusion

PLAN

Introduction
Pathogenesis
Classification
Types
Conclusion

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INTRODUCTION Acute myeloid leukemia (AML), also known as acute myelogenous leukemia

INTRODUCTION

Acute myeloid leukemia (AML),
also known as acute myelogenous leukemia or acute

nonlymphocytic leukemia (ANLL),
is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells.
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Pathogenesis

Pathogenesis

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Modern classification schemes for AML recognize the characteristics and behavior of

Modern classification schemes for AML recognize the characteristics and behavior of

the leukemic cell (and the leukemia) may depend on the stage at which differentiation was halted.
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Classification

Classification

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M0-M3 This scheme takes into account the degree of maturation M0

M0-M3

This scheme takes into account the degree of maturation

M0 acute myeloblastic leukemia,

minimally differentiated 5%
M1 acute myeloblastic leukemia, without maturation 15%
M2 acute myeloblastic leukemia, with granulocytic maturation t(8;21)(q22;q22), t(6;9) 25%
M3 promyelocytic, or acute promyelocytic leukemia (APL) t(15;17) 10%
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Minimally differentiated acute myeloblastic leukemia(M0)

Minimally differentiated acute myeloblastic leukemia(M0)

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Acute myeloblastic leukemia without maturation(M1)

Acute myeloblastic leukemia without maturation(M1)

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[ACUTE MYELOGENOUS LEUKEMIA, M1, BLOOD]. AML-M1 is defined by presence of

[ACUTE MYELOGENOUS LEUKEMIA, M1, BLOOD]. AML-M1 is defined by presence of

more than 90% myeloblasts in blood and/or bone marrow and lack of any recurring chromosomal abnormalities such as t(8;21), t(15;17), inv(16) or t(16;16)(p13;q22). The distinction between AML-M1 and AML-M2 not otherwise specified can be arbitrary than real since it merely depends on the blast count. AML-M1 is also known as AML without maturation. Most blasts are large and typical of myeloblasts with prominent nucleoli.
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[ACUTE MYELOGENOUS LEUKEMIA, M1, BLOOD]. The defining feature of a myeloblast

[ACUTE MYELOGENOUS LEUKEMIA, M1, BLOOD]. The defining feature of a myeloblast

is fine nuclear chromatin and scant to moderate amount of cytoplasm. Note that myeloblasts may not show any cytoplasmic granules or Auer rods as in this case. The correct identification rests upon immunophenotyping which shows expression of myelomonocytic antigens such as CD13, CD15, CD33, CD117, and myeloperoxidase. The blasts generally also express CD34 and HLA-DR.
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[ACUTE MYELOGENOUS LEUKEMIA, M1, BLOOD]. Multiple myeloblasts are shown with one

[ACUTE MYELOGENOUS LEUKEMIA, M1, BLOOD]. Multiple myeloblasts are shown with one

myeloblast containing several fine rods-like structures called Auer rods. Auer rods are only seen in acute leukemias of myeloid differentiation.
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Acute Myeloid Leukemia with Maturation (AML-M2)

Acute Myeloid Leukemia with Maturation (AML-M2)

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Acute promyelocytic leukemia M3

Acute promyelocytic leukemia M3

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[AML-M3]. Acute myelogenous leukemia, M3 type, also known as acute promyelocytic.This

[AML-M3]. Acute myelogenous leukemia, M3 type, also known as acute promyelocytic.This

case illustrates hypergranular morphology with most cells containing abundant large granules (arrows). Note the lack of more mature myeloid elements, such as metamyelocytes, bands, and segmented neutrophils. Also note the lack of erythroid elements. Although most cases show Auer rods, this particular case did not contain any Auer rods. The lack of Auer rods is a rare but well documented finding. This case had t(15;17) in all 20 metaphase cells and was also positive for PML-RAR fusion transcript by FISH study.
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[AML-M3].This photomicrograph shows another important morphologic feature of hypergranular type; specifically,

[AML-M3].This photomicrograph shows another important morphologic feature of hypergranular type; specifically,

not only intact cells with abundant granulation are identified (arrow) but many ruptured cells are also seen releasing their granules free onto the slide (four arrowheads). The leukemic cells appear to be more fragile than normal promyelocytes and break apart upon smearing on the slides. In the absence of Auer rods, presence of abundant free large granules helps in differentiating leukemic promyelocytes from normal promyelocytes.
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AML-M3. This image depicts another morphologic feature of acute promyelocytic leukemia,

AML-M3. This image depicts another morphologic feature of acute promyelocytic leukemia,

that is, polarity of cytoplasmic granulation. In many cells the granules tend to polarize toward one portion of the cytoplasm and the nucleus on the opposite side (arrows). In normal promyelocytes the granules are distributed rather evenly throughout the cytoplasm and polarization is not a distinct and obvious feature. When cytoplasmic granulation is heavy and polarized it is a good telltale morphologic sign of acute promyelocytic leukemia in the appropriate clinical context.
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AML-M3. Acute promyelocytic leukemia often shows cells having dumbbell shaped or

AML-M3. Acute promyelocytic leukemia often shows cells having dumbbell shaped or

convoluted nuclear lobes (arrows). This feature is more common with hypogranular/microgranular form than hypergranular type but a few cells can usually be found in the hypergranular type as well. Normal promyelocytes DO NOT have dumbbell shaped or convoluted nuclear lobes.
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AML-M3. Although most cells may show the hypergranular morphology (arrow), some

AML-M3. Although most cells may show the hypergranular morphology (arrow), some

cells can have a hypogranular/microgranular or typical blast morphology with fewer and finer granules and fine chromatin (curved arrows). When most cells show typical blast morphology, distinction from other acute myelogenous leukemia is difficult and the final diagnosis rests upon demonstration of the typical t(15;17) or positive FISH result for PML-RAR
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M4-M7 Lineage of the leukemic blasts: M4 acute myelomonocytic leukemia inv(16)(p13q22),

M4-M7

Lineage of the leukemic blasts:

M4 acute myelomonocytic leukemia inv(16)(p13q22), del(16q) 20%
M4eo myelomonocytic together with bone

marrow eosinophilia inv(16), t(16;16) 5%
M5 acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b) del (11q), t(9;11), t(11;19) 10%
M6 acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) 5%
M7 acute megakaryoblastic leukemia t(1;22) 5%
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involves an uncontrolled proliferation of myeloblasts and monoblasts Acute myelomonocytic leukemia

involves an uncontrolled proliferation of myeloblasts and monoblasts

Acute myelomonocytic leukemia

More than 20% of

the non-erythroid cells are monoblasts.
Monoblasts (like their mature counterpart, monocytes) have convoluted nuclei (A).
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Acute monocytic leukemia Note the nuclear folds and the relatively large

Acute monocytic leukemia

Note the nuclear folds and the relatively large nucleoli

typical of monoblasts at right.

blast cells in the bone marrow and blood precursors are represented essentially by monocytes.

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Acute erythroid leukemia myeloproliferation is of erythroblastic precursors

Acute erythroid leukemia

myeloproliferation is of erythroblastic precursors

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M6b (Pure erythroid leukemia) 80% erythroid precursors ranging from proerythroblasts to

M6b (Pure erythroid leukemia)
80% erythroid precursors ranging from proerythroblasts to

late polychromatophilic erythroid precursors (arrows).

Types

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Acute megacaryoblastic leukemia majority of the blasts are megakaryoblastic How looks megacaryoblasts?

Acute megacaryoblastic leukemia

majority of the blasts are megakaryoblastic

How looks
megacaryoblasts?

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Diagnosis requires more than 20% Blasts in the marrow/ peripheral blood

Diagnosis requires more than 20% Blasts in the marrow/ peripheral blood

with more than 50% demonstrating megakaryocytic derivation by morphology

20%

50%

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AML-M7, bone marrow section Megacaryoblasts are: Medium or large shaped Huge nuclei Light basophilic cytoplasm

AML-M7, bone marrow section

Megacaryoblasts are:
Medium or large shaped
Huge nuclei
Light

basophilic cytoplasm
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Causes GATA-1 is a protein that in humans is encoded by

Causes

GATA-1 is a protein that in humans is encoded by the GATA1 gene
Risk group: Children

with Down Syndrome
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Difference

Difference

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Classification is based on the type of cell from which the

Classification is based on the type of cell from which the

leukemia developed and its degree of maturity.
This is done by examining the appearance of the malignant cells with light microscopy and/or by using cytogenetics to characterize any underlying chromosomal abnormalities.

Conclusion