This document provides information about acute leukemias. It begins by defining leukemia as a stem cell or precursor disorder characterized by malignant proliferation of immature blood cells. It then discusses the key points of acute leukemias, including that they are usually aggressive diseases that affect the ability to produce normal blood cells. The document goes on to describe the classification, pathogenesis, clinical manifestations, prognosis, and immunophenotypes of the different subtypes of acute myeloid leukemia. It also compares acute and chronic leukemias and discusses acute lymphoblastic leukemia.
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AML vs ALL 5th Semester
1. NCS
University System
A Project of NCS Education System
Tanveer Tara
Senior Lecturer
Bachelor of Science in MLT
Masters of Science in Hematology
3. Leukemia:
All leukemia's are stem cell/ and or precursor of HSC
disorders characterized by malignant neoplastic
proliferation and accumulation of immature and
nonfunctional haemopoietic cells in the blood and bone
marrow.
4. Conti…
• Leukemia's are cancer found in the blood cells.
• Acute leukemia are usually aggressive disease.
• They are classified by how quickly they progress and what
type of cell they affect.
• Leukemia affects ability to produce normal blood cells.
• Bone marrow makes abnormally large number of immature
white blood cells called blasts.
7. Comparison of acute and chronic leukemia
FeaturesFeatures AcuteAcute ChronicChronic
AgeAge All agesAll ages AdultsAdults
Clinical onsetClinical onset SuddenSudden InsidiousInsidious
Course ofCourse of
diseasedisease
Week or monthsWeek or months Months to yearsMonths to years
Predominant cellPredominant cell Blast ,someBlast ,some
mature formsmature forms
Mature formsMature forms
AnemiaAnemia Mild – severeMild – severe MildMild
ThrombocytopeniaThrombocytopenia Mild – severeMild – severe MildMild
WBCWBC VariableVariable IncreasedIncreased
8. Pathogenesis of acute leukaemia
• Acute leukaemias are usually aggressive
diseases in which malignant transformation
occurs in the haemopoietic stem cell or early
progenitors.
• Genetic damage is believed to involve several
key biochemical
a.an increased rate of proliferation;
b.reduced apoptosis
c. a block in cellular differentiation.
9. Acute Leukaemogenesis
• Malignant transformation occurs as a result of the
accumulation of genetic mutations .
• Genes involved in the development of cancer are
divided broadly into two groups:
a. Oncogenes
b. Tumour-suppressor genes
12. Infiltration of tissues/organs
• Enlargement of liver, spleen, lymph nodes
• Gum hypertrophy
• Bone pain
• Other organs: CNS, skin, testis, any organ
13. ,
• Accumulation of blasts in microcirculation with
impaired perfusion.
• Lungs: hypoxemia, pulmonary infiltrates
• CNS: stroke
16. Acute myeloid leukaemia
• Acute myeloid leukaemia (AML) has an
incidence of 2 – 3 per 100 000 per annum in
children, rising to 15 per 100 000 in older
adults
18. Classification of Leukemia
WHO classification (Newer)
• Incorporates and interrelates morphology, cytogenetics,
molecular genetics, and immunologic markers.
• 20% blast in blood and bonemarrow.
FAB classification (Older)
• based upon morphology as determined by the degree of
differentiation along different cell lines and the extent
of cell maturation.
• 30% blast in blood and bone marrow.
19. FAB Classification of AML
M0: Minimally differentiated
M1: Myeloblastic leukemia without maturation
M2: Myeloblastic leukemia with maturation
M3: Hypergranular promyelocytic leukemia
M4: Myelomonocytic leukemia
M5: Monocytic leukemia
M6: Erythroleukemia (DiGuglielmo's disease)
M7: Megakaryoblastic leukemia
20. WHO classification of AML
1.Acute myeloid leukemia with recurrent genetic
abnormalities
• AML with t(8;21)(q22;q22), AML1 (CBF-
a)/ETO
• Acute promyelocytic leukemias [AML with
t(15;17)(q22;q11) and variants, PML/RAR-a]
• AML with abnormal bone marrow
eosinophils inv(16)(p13q22) or t(16;16)
(p13;q11), CBFb/MYH11X
• AML with 11q23 (MLL) abnormalities
21. 2 . AML with multilineage dysplasia
• With previous myelodysplastic syndrome
• Without previous myelodysplastic syndrome
3. AML & myelodysplastic syndromes, therapy-
related
• Alkylating agent-related
• Topoisomerase type II inhibitor-related (some
may be lymphoid)
• Other types
22. 4.AML not otherwise categorized
• AML minimally differentiated
• AML with maturation
• AML without maturation
• Acute myelomonocytic leukemia
• Acute monoblastic and monocytic
leukemia
• Acute erythroid leukemia
• Acute megakaryoblastic leukemia
• Acute basophilic leukemia
• Acute panmyelosis with myelofibrosis
5. Acute Biphenotypic Leukemias
26. Prognostic Factors in AML
• Favorable
– younger age (<50)
– WBC <30,000
– t(8;21) – seen in >50% with AML M2
– inv(16) – seen in AML M4 eos
– t(15;17) – seen in >80% AML M3
• Unfavorable
– older age (>60)
– Poor performance status
– WBC >100,000
– Elevated LDH
– prior MDS or hematogic malignancy
– CD34 positive phenotype, MRD1 postive phenotype
– del (5), del (7)
– trisomy 8
– t(6;9), t(9;22)
– t(9;11) – seen in AML M5
– FLT3 gene mutation (seen in 30% of patients)
27. Peripheral Blood AML
• Most patients with AML present with anemia normocytic normochromic.
• Thrombocytopenia
• Leukocytosis white blood cell count up to 200x109
• Large, sometimes hypogranular platelets can be seen, and functional defects can
contribute to hemorrhagic manifestations.
• Most patients are neutropenic, and morphologic abnormalities (hypogranulation,
nuclear hyperlobulation, Pelger-Huët anomaly) are often noted in the remaining
neutrophils.
• Blasts are predominant cells.
28. BM CHANGES IN AML
BM aspirates show
Hypercellularity
Cells predominantly myeloblasts
Immature granulocytes, erythroblasts, modest increase in plasma cells,
monocytes, megaloblastic erythroblasts,ring sideroblasts.
Erythropoeitic cells scanty, megaloblasts, ring sideroblasts found
Megakaryocytes reduced
Myelofibrosis can be seen
30. Blast classification
Type 1
Typical myeloblast with open chromatin and
prominent nucleoli, immature deep blue cytoplasm
without granules.
Type 2
Similar to type one + presence of up to 20 discrete
azurophilic granules.
Type 3
Similar to type one + numerous azurophilic granules.
31. AML-MO
• Distinguished by absence of visible granules in
cytoplasm of blast.
• Negative –ve reactions with cytochemical stains.
• Positive +ve for myeloid lineage markers.
CD13 CD33.
33. AML-M1
• AML variant and is most common in adults and in
infants less then 1 year.
• 50% cases show leucocytosis.
• Lack of cellular maturation.
• Predominant cell in peripheral blood is poorly
differentiated myeloblast.
• Vacuoles may be present.
• Platelet are generally decreased.
• A few blast may have scanty azurophilic granules or
Auer rod is present.
34. PB film of a patient with M1 AML showing blasts,some of
which are heavily vacuolated
35. AML-M2
• Presence of more differantiated cells in the bone marrow with
maturation.
• Condition is more common in adults.
• Leucocytosis in 50% of cases.
• Thrombocytopenia
• Myeloblast are predominant cell type in peripheral blood.
• Bone marrow is hypercellular.
• Azurophilic granules in variable amount.
• Auer rods a azurophilic granules are common.
Phi bodies:
Phi bodies are variant of auer rods but are smaller and not
necessarily in rod shaped.
36. BM film of a patient with M2 AML showing unusually heavy
granulation of neutrophils and precursors
37. AML-M3
• Typically seen in young adults.
• Sudden and severe progression.
• Cause acute DIC.
• DLC shows predominance of promyelocytes.
• Nucleus is very delicate sometime show foldings.
• Most common clinical finding is bleeding.
38. Auer rods
• Auer rods are red staining, needle-like bodies seen in the
cytoplasm of myeloblasts, and/or progranulocytes in certain
leukemias. Auer rods are cytoplasmic inclusions which result
from an abnormal fusion of the primary (azurophilic) granules.
•
40. AML-M4
• Both myelocytic and monocytic cells are present in peripheral
blood and bone marrow.
• Infilteration of leukemic cells in extramedullary sites is more
common.
• Serum and urine level of meuramidase are usually elevated
because of monocytic proliferation.
• Anemia
• Thrombocytopenia
• Cytochemical stains will demonstrate two cells population in
bone marrow.
42. AML-M5
• Usually seen in children and young adults.
• Degree of gum hypertrophy ,lymph node ,CNS and extra
medullary infiltrates seen.
• Occasional episods of DIC.
• Moderately elivated serum and urine muramidase.
• More then 80% of non erythroid cells seen in BM are
monocytic .
44. AML-M5a
• Poorly differentiated.
• Monoblast account for 80% or more of all monocytic cells.
• Remeining 20% are monocytes.
• The monoblast are larger.
• Azurophilic granules may be present.
45. AML-M5b
• Well differentiated.
• More then 80% of monocytic cells in nonerythroid marrow.
• The remaining cells are promonocytic or monocytic.
• The percentage of blast is less then 30%.
• Fine azeurophilic granules are present.
46. AML-M6
• Predominant cells in the bone marrow is erythroblast.
• Predominant feature is anemia with striking
poikilocytosis and anisocytosis.
• The diagnosis of erythroleucaemia can be done if more
then 50% of bone marrow cells are erythroid and 30% of
remaining are blast.
• True erythro leukemia occurs when BM is replaced by
proliferating normoblast showing no maturation beyond
basophilic normoblasts.
47. PB film in a patient with M6 AML showing an abnormal
circulating erythroblast
48. AML-M7
Peripheral blood pancytopenia.
High peripheral blood blast count.
Micro megakaryocytes and undifferentiated blast.
Bone marrow reveals increased fibroblast.
Showing cytoplasmic budding.
52. • Leukaemia is the most common childhood
cancer and acute lymphoblastic leukaemia
(ALL) is the most common subtype,
accounting for 75 – 80% of all cases
53. FAB Classification of ALL
• L1—Mature-appearing lymphoblasts (T-cells or pre-B-cells)
small blast with High N:C ration.
• L2—Immature and pleomorphic (variously shaped)
lymphoblasts (T-cells or pre-B-cells) small and large blast
present with moderate N:C ration.
• L3— Lymphoblasts (B-cells; Burkitt's cells) are large and
uniform, deep basophilic cytoplasm, vaculation in cytoplasm
and low N:C ratio.
54. FeaturesFeatures L1L1 L2L2 L3L3
Cell sizeCell size Small, uniformSmall, uniform Large, oftenLarge, often
heterogeneousheterogeneous
Large, homogeneousLarge, homogeneous
NucleusNucleus Round, regularRound, regular Oval to round,Oval to round,
irregular cleftingirregular clefting
RoundRound
Amount ofAmount of
cytoplasmcytoplasm
ScantScant ModeratelyModerately
abundantabundant
Moderately abundantModerately abundant
Genetic materialGenetic material Dense, uniformDense, uniform variablevariable finely stippled andfinely stippled and
uniformuniform
NucleoliNucleoli Inconspicuous,Inconspicuous,
smallsmall
Prominent, largeProminent, large
1 - >11 - >1
Present, may bePresent, may be
prominentprominent
1- >1, vesicular1- >1, vesicular
cytoplasmcytoplasm
vacuolesvacuoles
OcassionalOcassional VariableVariable ProminentProminent
BasophiliaBasophilia SlightSlight VariableVariable PunctatePunctate
FrequencyFrequency 85%85% 15%15% 2%2%
FAB CLASSIFICATION ALL
55. • WHO has recognized just two groups of acute
lymphoblastic leukemias,
• precursor B-cell and
• precursor T-cell lymphoblastic
leukemia/lymphoma.
56. Precursor B lymphoblastic leukemia (B-ALL)/lymphoblastic
lymphoma (B-LBL)
• B-ALL comprises approximately 85% of all childhood ALL,
whereas B-LBL is a rare type of lymphoma and constitutes
approximately 10% of lymphoblastic lymphoma cases.
• is a malignancy where B lineage lymphoblasts predominate in
the bone marrow (B lymphoblastic leukemia).
• Sometimes there is primary involvement of lymph nodes or
extranodal sites (B lymphoblastic lymphoma).
• Greater than 20% of bone marrow cells
57. • However, the bone marrow aspirate typically
consists of almost entirely lymphoblasts at diagnosis.
• When the leukemic process is limited to a mass
lesion and less than 20% or fewer lymphoblasts are
seen in the marrow, the designation lymphoma is
used.
58. • The blood and bone marrow contains lymphoblasts
• with L1 or L2 morphology
• B-ALL may also develop in adults, and the prognosis is generally much poorer in
adults
Immunophenotype
• The lymphoblasts in B-ALL/LBL are uniformly TdT
positive and HLA-DR positive.
• The flow cytometric immunophenotype in most cases is positive for CD 10, CD19,
CD20, CD24, CD22, and CD79a
59. Precursor T lymphoblastic leukemia/lymphoma
• is a malignancy of lymphoblasts with pre-T markers predominating in the
bone marrow (T-ALL).
• When there is primary involvement of lymph nodes or extranodal sites, it
is termed T lymphoblastic lymphoma.
• T-ALL represents approximately 15% to 20% of all childhood ALL, is more
prevalent in adolescents than young children, and is seen more frequently
in males than females.
• often have L2 morphology
• less frequently, have L1 morphology
60. • The lymphoblasts in T-ALL are TdT,
cytoplasmic CD3, CD7, CD1, CD2, , CD5
positive
64. Peripheral Blood ALL
• WBCs
– Total cont elevated 50-60 x 109
/L to 100 109
/L
– Rarely more than 100 x 109
/L
– Lymphoblasts in large numbers
• RBCs
– Normocytic normochromic anaemia.
Thrombocytopenia.
65. BM CHANGES IN ALL
Marrow aspirates show:
Blast cell predominace. They are lymphoblasts which are
earliest identifiable precursor of lymphoid cells
Erythropeitic cells reduced
Dyserythropoiesis
Megakaryocytes reduced
66. ALL-L1
• This is the most common form found in children
and it has the best prognosis.
73. Aids in the diagnosis
Classification of the leukemias
Identification of the chemical components of
cells - is conducted to distinguish different types
of leukemia.
Cytochemistry
75. Leukemia,White Blood 75
Cytochemical differences in ALL & AML blasts
CYTOCHEMICAL STAINCYTOCHEMICAL STAIN ALL BLASTSALL BLASTS AML BLASTSAML BLASTS
MPOMPO NegativeNegative PositivePositive
SUDAN BLACK BSUDAN BLACK B NegativeNegative PositivePositive
PASPAS PositivePositive NegativeNegative
NON SPECIFICNON SPECIFIC
ESTERASEESTERASE
NegativeNegative PositivePositive
ACID PHOSPHATASEACID PHOSPHATASE PositivePositive NegativeNegative
76. Leukemia,White Blood 76
Biochemical tests
• Serum uric acid raised due to breakdown of leukemic
cells.
• Serum LDH may be raised
• Hypocalcaemia
• Hyperuricemia
• Increase K+
77. Terminal Deoxynucleotidyl Transferase
Terminal deoxynucleotidyl transferase (TdT) is an
intranuclear enzyme found in stem cells and immature
lymphoid cells within the bone marrow, but not in
mature B lymphocytes.
78. Significance of TdT
• It is present in 90% of acute lymphoblastic leukemias.
• Only 5%-10% of acute myeloblastic leukemias.
• It has also been demonstrated in 1/3 of cases of the blast
crisis stage of chronic myelogenous leukemia and is a good
prognostic indicator in these patients.
79. Imaging Studies
It is likely that the physician will want to perform imaging studies to
determine whether the leukemia has invaded other organs within the
body. Such studies will include:
• X-rays
• Computed tomography (CT or CAT)
• Magnetic resonance imaging (MRI)
• Radionuclide (radioactive atom)
• Ultrasound
81. Karyotyping
• A karyotype is the characteristic chromosome
complement of a eukaryote species.
• Its study is called karyotyping.
• The preparation and study of karyotypes is part of
cytogenetics.