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DeÞnitions

Important notes

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Leukemia
Neoplasm
¥ abnormal growth of tissue, which if it forms a mass, is commonly referred to as a tumour
¥ It can also be defined as: Dysregulated autonomous monoclonal proliferation of a transformed
cell.
¥ Autonomous means the neoplastic cell isnÕt dependent on external growth factor to regulate proliferation
¥ Monoclonal means that the neoplastic cells are derived from a single mother cell.
¥ Transformation refers to the change in phenotype due to a new genetic material (i.e mutation)

¥ The tumor can be either malignant or benign.

Benign vs. Malignant

¥ Benign neoplasms are:
- highly organized, well-differentiated cells
In benign, The process of neoplasia is dysregulated, but the
- does not spread or invade surrounding tissue. cells themselves are organized and differentiated

Mass effect:
¥ Although benign tumors will not metastasize, it can ÒpushÓ to surrounding structures causing secondary pathological
manifestations. They can compress tissues and may cause nerve damage, ischaemia, necrosis and organ damage.
¥ The mass effect of tumors are more prominent if the tumor is within an enclosed space such as the cranium, respiratory
tract ,sinus or inside bones.

¥ Malignant neoplasm has The abnormality can be morphological or functional

- abnormal proliferating cells
A benign neoplasm can progress to a malignant neoplasm
- often have the potential to metastasize.

¥ When the neoplasia arise from the cells of the blood it is called leukemias or lymphomas

Lymphoma (abnormal cells originate from lymph nodes)

¥ Abnormal proliferation of lymphoid cells within the lymphatic tissue or lymph nodes.
¥ These cells are capable of shifting to the circulation, then infiltrate to bone marrow
¥ The leukemic phase of lymphoma: is when the lymphoma affects the bone marrow and the
lymphoma cells are found in the peripheral circulation.
Leukemia (abnormal cells originate from bone marrow)
¥ The lymphoid and myeloid malignant bone marrow neoplasms are collectively known as
leukemia.

Although there is an increase in leukocytes (leukocytosis), these cells are functionally abnormal. Because of the ÒcrowdedÓ
bone marrow, the bone marrow is unable to produce normal cells properly, causing (normal cell cytopenia)

¥ The term leukemia is used when abnormal cells are seen in both the bone marrow and the
peripheral circulation.
¥ If the abnormal cells are found only in the bone marrow, the term aleukemic leukemia is used.
¥ If abnormal cells in bone marrow + circulation = leukemia
¥ Abnormal cells in bone marrow only = aleukemic leukemia

¥ It results in:
Failure of normal hematopoiesis, As the neoplastic cells population increases, normal cell
decreases resulting in cytopenias of normal blood cells. Causing:
- Infections secondary to granulocytopenia
- bleeding secondary to thrombocytopenia
- anemia subsequent to decreased normal RBCs (in erythroleukemia)

The two broad groups of leukemia are myeloid and lymphoid.

¥ If myelocytic cells or other cells derived from the common myeloid progenitor cell (CMP)
predominate, the disease is called myelogenous leukemia.
¥ If lymphoid cells predominate, the disease is called lymphocytic leukemia.
¥ These two groups are further classified based on the aggressiveness of the illness and degree
of differentiation of the leukemic cells into acute and chronic
tumor heterogeneity
¥ Tumour heterogeneity means that different tumour cells can show distinct morphological
features (including difference in gene expression, metabolism, motility, proliferation, and metastatic potential.)

¥ Two main mechanisms have been conceptualized to explain intertumoral heterogeneity:

a. different genetic or epigenetic mutations

occurring within the same target cell result
in different tumour phenotypes

Þgure (a): that the same cell was affected by different oncogenes,
resulting in different tumor morphology (tumor heterogeneity)

¥ Epigenetic mutations are the ones that affect gene

expression without any change in DNA sequence
¥ oncogene is a mutated gene that contributes to the
development of a cancer

b. different tumour subtypes arise from distinct cells within the tissue that serve as the cell of
origin

Fig (b): the same oncogene affecting different stages

of cell maturation, causing tumor heterogeneity

Within the system, only HSC possess the ability of both multi-
potency and self-renewal.
Acute Leukemia (AL)
¥ Acute leukemias are usually aggressive diseases in which malignant transformation occurs in
the hemopoietic stem cell or early progenitors.
¥ There will be an increase in blast cells and some mature forms but an apparent decrease in
the intermediate maturation stages.
the increase in blasts without an increase in later stages of maturation indicates proliferation without maturation

¥ The neoplastic blasts accumulate in the bone marrow and spill over into the circulation
producing leukocytosis with normal cell cytopenia
¥ The etiology of AL was hypothesized to be a Genetic damage resulting in
- an increased rate of proliferation
The net effect is expansion of the leukemic clone and a
- reduced apoptosis decrease in normal cells
- a block in cellular differentiation.
¥ The dominant clinical features:
- Bone marrow failure caused by accumulation of blast cells
- organ infiltration also occurs.
¥ In acute leukemia, blood smear reveals the presence of many undifferentiated or minimally
differentiated cells.
¥ If untreated, acute leukemias are usually rapidly fatal but they may be easier to cure than
chronic leukemias.

Subtypes of Acute Leukemia

1- Acute myeloid leukemia (AML) when it develops from the myeloid lineage which can be:
- granulocytic (PMNs). - monocytic. - erythrocytic. - megakaryocytic
AML can also be reffered to as acute
nonlymphocytic leukemia (ANLL).

2- Acute lymphocytic leukemia (ALL) involving lymphocytic lineage (CLP): T or B cell neoplasm.

How to differentiate T cell neoplasm ?

T cells have CD3 marker
How to differentiate B cell neoplasm ?
B cells have CD19 marker

In both cases, Blasts > 20%

FAB classification of leukemia
¥ Classified based on morphology (including cell size, prominence of nucleoli, and the amount and
appearance of cytoplasm)
¥ In AML, the 8 subtypes differ in degree of
maturation (discussed in detail later)

Acute myeloid leukemia (AML)

AML incedince Take your time reading the table

¥ AML is the most common form of acute leukemia in adults and becomes
increasingly common with age with a median onset of 65 years.
¥ It forms only a minor fraction (10 Ð 15%) of the leukemias in childhood.

AML (Auer rod)

¥ Auer rods are clumps of azurophilic (primary) granular material that form elongated needles
seen in the cytoplasm of leukemic blasts (promyelocytes)
¥ They can be seen in:
- AML M2 and M3
- high grade myelodysplastic syndromes
- myeloproliferative syndromes

From the prominent nucleoli, immature chromatin and high N:C ratio, we can conclude that
this cell has poor differentiation

Before going any further, i advise you to revise Òneutrophil

precursorsÓ so you can fully understand the following
AML M0 Òminimally differentiated AMLÓ
¥ Undifferentiated myeloblast (most common in adult patients)
¥ small to medium-sized round cells with an eccentric nucleus.
¥ nucleus has flattened shape and was sometimes lobulated or cleaved
¥ The cytoplasm was lightly basophilic without granules.
¥ Auer rods are not found

AML M1 ÒAML with no maturationÓ

¥ usually a poorly differentiated myeloblast
¥ prominent nucleoli
¥ Auer rods are found in the blast of 50% of the M1 patients
¥ Few granules
¥ all aged groups with highest incidence seen in adult and in infants
youngr than 1 year

AML M2 ÒAML with maturationÓ

¥ maturation at or beyond the promyelocyte stage
¥ Myeloblast can usually be found in the blood smears and may be the predominant cell type.
¥ PseudopelgerÐHuet and hypogranular neutrophils being most common cells are seen in M2.
PseudopelgerÐHuet: neutrophils with abnormal nuclear segmentations (being bilobed instead of the normal trilobed shape) and
unusual structure (coarse and lumpy), it can be called ÒdumbbellÓ or ÒpeanutÓ shaped

¥ The monocytic component is less than 20%, differentiating M2 from M4.

¥ Auer rods can be present and Granules are common

Pseudopelger-huet/ dumbbell/ peanut neutrophil

AML M3 ÒAcute promyelocytic leukemia (APL)Ó

¥ The blasts are large with abundant cytoplasm, and the nucleus is usually irregular. The
nucleus is often bilobed or markedly indented
¥ a nucleolus can be seen in each lobe.
¥ The cytoplasm is completely occupied by closely packed large granules
¥ Cells containing bundles of Auer rods "faggots" randomly distributed in the cytoplasm are
characteristic, but are not present in all case
¥ Auer rods are strongly present
AML M4 ÒAcute myelomonocytic leukemia (AMML)Ó
¥ increased proportion of leukemia monocytic cells in the bone marrow or blood or both
¥ monocytic cells are increased to 5000/uL or more

AML M5 ÒAcute monoblastic leukemia (AMoL)Ó

¥ 80% or more of all nonerythroid cells in the bone marrow are monocytic cells.
¥ This class is divided into:
- M5a acute monoblastic leukemia, in which monoblasts predominate (>80%)
- M5b or acute monocytic leukemia, (Characterized by the presence of all developmental
stages of monocytes Òmonoblast, promonocyte and monocyteÓ)

M6 ÒErythroleukemia"
¥ Rare
¥ Nucleated red cells demonstrate abnormal nuclear configuration
¥ The most dominant changes in the peripheral blood are anemia with
sticking poikilocytosis and anisocytosis
¥ The erythroblast is abnormal with bizarre morphologic features.
¥ Giant multilobular or multinucleated forms are common.
Remember, bone marrow crowding causes cytopenia

M7 Acute megakaryoblastic leukemia (AMkL)

¥ Rare
¥ micromegakaryocytes and undifferentiated blasts
¥ cytoplasmic protrusion or budding

In Lab, we can differentiate and classify various cells by:

1- microscopic examination: to differentiate according to morphology, for example, we can differentiate monocytes from
lymphocytes by observing the morphology of the nucleus
But in some cases, it can be hard to differentiate various stages or different types only by using microscope, so we resort to
other strategies like:
2- markers and ßow cytometry (immunophenotype), we discussed previously that different stages of neutrophils had different
markers, this applies to other cell types as well. Immunophenotype can also differentiate cell types (for example, T cells are
characterized by CD3 while B cells are characterized by CD19)
3- cytochemical staining (histopathology): for example, we use Sudan black to tell apart myeloid cells from lymphoid cells,
myeloperoxidase can be used as well to distinguish myelogenous from monocytic leukemia
Lab Findings of AML
1- Peripheral Blood
¥ Although it is traditional to describe leukemias as having elevated WBC count , 50% of cases
can have decreased counts or counts within the normal range.
¥ the presence of blasts on the blood smear suggests Acute Leukemia diagnosis.

according to FAB, AL is >30% blasts in

peripheral blood or bone marrow

RBC inclusions:
¥ Howell jolly bodies: remnant DNA, indicates splenic dysfunction
¥ Pappenhiemer bodies
¥ Basophilic stippling: can be seen in lead poisoning too
Maturation defect indicates bone marrow failure

2- bone marrow
¥ a spicemen can be taken by either BM aspiration or BM biopsy
¥ Hypercellular with decreased fat content (crowded)
¥ Predominance in blasts and sometimes increased fibrosis
¥ Auer rods are present in about half of cases
¥ cells can be clumped together , occasionally forming sheets of infiltrate that disrupt the
marrow architecture

3- Others
1- Hyperurecemia (because of increased cellular destruction Ñ> nucleic acid destruction)
2- Elevated Lactate Dehydrogenase
3- Hypercalcemia
4- Elevated serum and urine Muaramidase are typical findings in leukemia with monocytic
component.
Muramidase is a bactericidal enzyme that is found in some hematopoietic cells. It is
primarily present in granulocytes, monocytes, and histiocytes.

¥ All thes findings reflect the increased proliferation and turnover of cells.
Clinical Manifestations of AML
¥ AL occurs at any age , but more common in adults (50-60yrs).
¥ Signs and symptoms are due to cytopenia (anemia/granulocytopenia/thromphocytopenia) &
tissue infiltration (the blasts Òspill overÓ from the bone marrow to circulation and organs)
Common Manifestations:
One: anemia
1- Pallor 2- Anemia 3- Fatigue/Malaise 4- Palpitation 5- Dyspnia
Two: thrombocytopenia
6- Bleeding(GI,UT,Nose)
Three: granulocytopenia
7- Fever and infections
Four: infiltration to tissues
8- Lymphadenopathy 9- Gum Hyperplasia
Five: others
10- Bone Pain: because of increased production of myeloblasts causing bone marrow expansion
11- Weight loss: because rapidly dividing cancer cells use up large amounts of energy
12- hepato and splenomegaly due to increased destruction

Clinical manifestations related to subtypes of AML

Chronic Leukemia
¥ Characterized by leukocytosis.
¥ Although blasts may be present in the peripheral blood, there is a predominance of more
mature cells.

Subtypes of Chronic Leukemia

¥ The bone marrow in chronic leukemia exhibit an accumulation of differentiated lymphocytic
(Chronic Lymphocytic Leukemia- CLL) or myelocytic (Chronic Myelocytic Leukemia- CML).
¥ The differential count of bone marrow and peripheral blood involve all STAGES of maturation
but with predominance of more mature forms (blasts < 20%)

Chronic Myeloid Leukemia (CML)

¥ is when the bone marrow exhibit an accumulation of differentiated myelocytic lineage.
¥ may occur at any age.

CML etiology
¥ CML is caused by a chromosomal defect, which is a translocation, in which parts of two
chromosomes, 9 and 22, swap places, the result is a chromosome called the Philadelphia
chromosome. (t(9:22))

A fusion gene is created by juxtapositioning the (Ableson leukemia

virus) ABL gene on chromosome 9 to a part of the (Breakpoint
Cluster Region) BCR gene on chromosome 22. This is a translocation
creating an elongated chromosome 9 (der 9), and a truncated
chromosome 22 (Philadelphia chromosome).
pathogenesis of CML
1- BCR gene on chromosome 22 fused to the ABL gene on chromosome 9
*The ABL gene expresses a tyrosine kinase, The activity is typically regulated in an auto-
inhibitory fashion
2- the BCR-Abl transcript is also translated into a tyrosine kinase, but the BCR-Abl fusion gene
codes for a protein that is "always on" or continuously activated leading to unregulated cell
division (i.e. neoplasia).
Ph chromosome is found on myeloid, monocytic, erythroid, megakaryocytic, B-cells and sometimes T-cell proof that CML derived
from pluripotent stem cell

STAGING OF CML
¥ Three main stages, determined by percentage of blast cells in the blood
One: Chronic Phase
¥ Patient usually diagnosed
¥ Fewer than 10% of cells in blood and bone marrow are granulocytes
¥ Prognosis: (with imatinib) 5yr: 70%, 10yr: 30-40%

Two: Accelerated phase

¥ Median duration is 3.5 Ð 5 yrs before evolving to more aggressive phases
¥ Clinical features
- Increasing splenomegaly refractory to chemo
- Increasing chemotherapy requirement
¥ Lab features
- Blasts > 15% in blood
- Blast & promyelocyte > 30% in blood
- Basophil 20% in blood (specific to accelerated phase)
- Thrombocytopenia
- Cytogenetic: clonal evolution Somatic evolution is the accumulation of mutations in
the cells of a body during a lifetime, itÕs important in
Three: Blastic phase
the development of cancer
¥ Resembles acute leukemia
¥ Diagnosis requires > 30% blast in marrow
¥ 2/3 transform to myeloid blastic phase and 1/3 to lymphoid blastic phase
¥ Survival : 9 months lymphoid vs 3 months myeloid (CML can turn to CLL)
Summary:

Clinical features of CML

¥ Disease is biphasic, sometimes triphasic
¥ 40% asymptomatic
¥ Splenomegaly often massive
¥ Symptoms related to hypermetabolism:
- Weight loss - Anorexia - Lassitude - Night sweats Lassitude: a state of physical or
¥ Features of anemia mental weariness; lack of energy.

Ð Pallor - dyspnia - tachycardia

dyspnia is the most common reason for visiting a
¥ Abnormal platelet function hospital accident and emergency department.
- Bruising - epistaxis - menorrhagia
¥ Hyperleukocytosis
Epistaxis: bleeding from the nose.
Ð thrombosis Menorrhagia: abnormally heavy bleeding at menstruation.
Ð Increased purine breakdown : gout
Ð Visual disturbances
Gout: a disease in which defective metabolism of uric acid
Ð Priapism causes arthritis, especially in the smaller bones of the feet,
deposition of chalk-stones, and episodes of acute pain.
Lab features
¥ Peripheral blood film
Ð Leukocytosis (usu >25 x 109/L, freq> 100 x 109/L
Ð Anemia
Ð WBC differential shows granulocytes in all stages of maturation (promyelocytes, myelocytes,
metamyelocytes and band and segmented neutrophils)
Ð Basophilia
Ð thrombocytosis

How to diagnose?

In the left Þg.

1- in the given blood Þlm there is a huge increase in WBCs indicating leukocytosis
2- in an inßammatory process there will be an increase in segmented neutrophils and
bands only, however, this blood Þlm shows promyelocytes and metamyelocytes in
addition to bands and segmented N. which rules out inßammation
3- in AML, the blasts are > 30%, while in CML blasts are <20%, in the blood Þlm,
among almost 23 neutrophil precoursors, there are 0 myeloblasts which makes it more
probable to be CML

ÑÑ promyelocyte (2) ÑÑ myelocyte (5) ÑÑ metamyelocyte (7) ÑÑ band (5) ÑÑ segmented N. (4)

Like the previous Þgure, this is CML (leukocytosis and showing all stages),
however, this is a more progressed stage, this is because of increased blast &
promyelocyte proportion (7 out of 22 = 32%) Òless differentiatedÓ and the blast
percentage is 2/22 = 9%
itÕs not AML (blasts <30%)

ÑÑ myeloblast (2) Òsee the prominent nucleolus ÑÑ Ó

Acute Lymphoblastic Leukemia (ALL)
¥ Malignant neoplastic proliferation and accumulation of immature and dysfunctional
hematopoietic cells in the bone marrow.
¥ Presence of >20% lymphoblasts is a MUST in diagnosis.
¥ TdT stain positive ( a DNA polymerase specific to lymphoblasts).

Incidence
¥ 80% of leukemias
¥ Girl to boy ratio is 1 : 1.2
¥ Peak incidence 2 Ð 5 years
¥ Incidence in white children is twice as high as in nonwhite children

Clinical manifestation
¥ history and symptoms reflect:
1. the degree of bone marrow infiltration by leukemic cells
2. the extramedullary involvement of the disease
¥ the duration of symptoms is days to several weeks, occasionally several months
¥ The symptoms depend on the degree of cytopenia:
- anemia: pallor, fatigue, tachycardia, dyspnea, cardiovascular decompensation
- leukopenia:infections, temperature elevation
- thrombocytopenia: petechiae, mucosal bleeding, epistaxes, prolonged menstrual bleeding
¥ Specific signs and symptoms
- Eye: bleeding, infiltration of local vessels

- CNS : at time of diagnosis less than 5% have CNS leukemia with meningeal signs (morning
headache, vomiting, papilla edema, focal neurological signs)
Focal neurological signs: impairments of nerve, spinal cord, or brain function
that affects a speciÞc region of the body, e.g. weakness in the left arm

- Ear, nose, throat:

= lymph nodes infiltration (isolated or multiple)
= Mikulicz syndrome (infiltration of salivary glands, tear glands and/or parotid gland)
 - Skin: maculopapular skin infiltration, often of deep red color (infants)

- Cardiac involvement:
= leukemic infiltration or hemorrhage
= occasionally cardiac tamponade due to pericardial infiltration
= tachycardia, low blood pressure or other signs of cardiac insufficiency

Tamponade
- Mediastinum:
= enlargement due to leukemic infiltration by lymph nodes and /or thymus (observed in

T-cell leukemia)

- Pleural effusion

- Kidney enlargement

- Lymphadenopathy Hepatosplenomegaly Lymphadenopathy

- Gastrointestinal involvement:
= hepato and/or splenomegaly

- Testicular involvement: enlargement of one or both testes without pain , hard consistency
- Penis: priapism is occasionally associated with elevated WBC
- Bone and joint involvement:
= bone pain initially present in 25 % to 50% of patients
= bone or joint pain, sometimes with swelling and tenderness due to leukemic
infiltration of the periosteum.
= Differential diagnosis: rheumatic fever, rheumatoid arthritis
= radiological changes:
Diffuse demineralization : a process in which calcium is removed from bones
diffuse demineralization, osteolysis,
Laboratory findings
¥ Blood
- Red cells:
-hemoglobin : normal/ moderate /markedly low
-low number of reticulocytes (bone marrow failure)
- White blood cell :
- normal/ low/ high
- in children with high WBC- leukemic blast cells present
- Platelets:
-usually low (thrombocytopenia)
- The excess of blasts reflect proliferation of abnormal
malignant clone which fail to
undergo For example, 60% of A.L.L. patients presented with fever
maturation.

Leukocyte count indicates the excess of blasts, this reßects the aggressiveness and
prognosis of the disease (less leukocyte count is good prognosis)

This also means that having leukemia doesnÕt mean an absolute increase in leukocytes

88% of A.L.L patients have anemia

80% of patients have thrombocytopenia

¥ Coagulopathy: Although there is thrombocytopenia,

some patients can suffer from
-in children with hyperleukocytosis
thrombosis, this is because of
-more common in AML increased WBC count, leading to
-low levels of prothrombin, fibrinogen, factors V, IX, and X increased viscosity of the blood,
which increases thrombosis
may be present

¥ Chemistry:
-the serum uric acid is often high initially
Uric acid turnover is produced by the breakdown of the cellular nucleic acids of leukocytes ,
and may be a marker of disease aggressiveness

- the serum potassium level may be high (cell lysis)

-serum hypocalcemia or hypercalcemia (in marked leukemic bone infiltration)
- abnormal liver function Ñ> increased level of transaminases
 A.L.L record starts here:
¥ Bone marrow analysis: https://drive.google.com/Þle/d/136Oxzki9J6vPwtljSTG4_pTjbVyb4xjw/
view?usp=drivesdk
- blasts > 25%
- characterize the blast cells
- determine the degree of reduction of normal hematopoiesis
- morphological, immunological, biochemical, and cytogenetic analyses

¥ Differential diagnosis

myelodysplastic syndrome (MDS)

¥ is one of a group of cancers in which immature blood cells in the bone marrow do not mature, resulting in normal cell
cytopenia.
¥ symptoms may include feeling tired, shortness of breath (anemia), bleeding disorders (thrombocytopenia)or frequent infections
(granulocytopenia)
¥ Some types may develop into acute myeloid leukemia.
¥ Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals

- aplastic anemia, myelodysplastic syndrome, neoplastic infiltrations (neuroblastoma, NHL)2

Acute lymphoid leukemia (ALL) subtypes (according to FAB)

Burkitt's type: is a cancer of

the lymphatic system,
particularly B lymphocytes
ALL1 lymphoblasts
L1 lymphoblasts are small cells with homogenous population, characterized by:
¥ high N:C ratio.
¥ pale blue cytoplasm is scanty and is limited to a small portion of the perimeter of the cell.
¥ The cells have indistinct nucleoli and nuclear membranes that vary from round to clefted
¥ Approximately 85% of children with ALL have predominant L1 morphology

ALL2 lymphoblasts
L2 lymphoblasts are larger, often in a more heterogeneous population
¥ lower nucleus-to-cytoplasm ratio
¥ prominent nucleoli (often with perinuclear chromatin condensation) and nuclear membranes
that may be reniform or irregular.
¥ 14% of children with ALL have L2
¥ the L2 subtype is more common in adults

They may be morphologically indistinguishable from the M1 variant of

myeloid leukaemia, and the differentiation must be made primarily by
myeloperoxidase (MPO) staining; the M0 variant of myeloid leukaemia,
which is MPO negative, may be indistinguishable from ALL without the
immunophenotype.

ALL3
L3 lymphoblasts is a heterogeneous group of cells identical to Burkitt-like leukaemia and
characterized by deeply basophilic cytoplasm and prominent cytoplasmatic vacuolization.
¥ 1% of children with ALL have L3
Summary

WHO classification (according to cytogenetic morphology)

The WHO classification defines two subgroups of ALL
1) Precursor B- and T-cell neoplasms (which includes the FAB categories of L1 and L2)
2) Burkitt type ALL (FAB category L3)

One: Precursor B-cell leukemia

Stages of Precursor B-cell leukemia

1- pro B: CD19+ and CD79a+
2- intermediate pre-B stage: also called common ALL (CALL): CD10 (CALL antigen ÒCALLAÓ)
3- pre B stage: CD20 / CD22 / and cytoplasmic mu chain (cytm)

Cytogenetic abnormalities
¥ Cytogenetic abnormalities associated with B-ALL include translocations, hypodiploidy, and
hyperdiploidy
¥ The most common translocation in childhood B-ALL, present in 25% of the cases, is t(12;21)
(p13;q22), producing the TEL-AML1 fusion gene.
The translocation happens during fetal hemopoiesis, this
explains the early onset of leukemia

¥ Other cytogenetic abnormalities include t(9;22) (q34;q11.2) (BCR/ABL) which is more common
in adults (10-15%)
Q: Also known as????
A: Philadelphia chromosome
Two: Precursor T-Cell Leukemia
¥ is a neoplasm of lymphoblasts committed to the T-cell lineage, involving the bone marrow and
peripheral blood
¥ T- ALL accounts for about 15% of childhood ALL.
¥ The lymphoblasts in T-ALL are TdT+, CD7+ and They can have variable expression of CD1, CD2,
CD4, Cd5, CD8, and CD10.

Precursor T-Cell Leukemia Stages

1- cortical stage of thymocyte differentiation: lymphoblasts frequently coexpress CD4 and CD8
2- At the medullary stage of differentiation: the cells are either CD4+ or CD8+

Cytogenetic abnormalities
¥ Cytogenetic studies reveal translocations in T-ALL :About one-third of the cases of T-ALL
have translocations involving the alpha and delta T-cell receptor loci (14q11.2),,, the beta
locus (7q35) or the gamma locus (7p14Ð15)

Three: Acute Lymphoblastic LeukemiaÑBurkitt Type

¥ is rare form of ALL occurs in both adults and children
¥ all cases have a translocation of the MYC gene on chromosome 8 (8q24) to the heavy chain
region on chromosome 14 [t(8;14)]
Prognostic factors
¥ Prognostic factors are measurements that can often be used to predict the natural history of
the tumor.
¥ treatment based on prognostic factors plays an important role in the management of cancer.

Indicates disease aggressiveness

There is maturation meaning itÕs good

because decreased maturation indicates
more aggressive disease

Visceromegaly is enlargement of the

organs inside the abdomen, such as the
liver, spleen, stomach, kidneys, or pancreas

Hyperploid is a chromosomal abnormality in that is characterized by an addition of chromosomes that results in a chromosome
number that is not an exact multiple of the haploid number.

Staining:
ALL: periodic acid Schiff (Block +ve), + Tdt
AML: + Sudan black, + peroxidase
Cytogenetic characterization
ALL can be classified into 4 subtypes based on the modal number of chromosomes:
1. Hyperdiploid with more than 47 chromosome (35-45% of cases, defined by a DI greater than
1.0)
DI: DNA index = no. of chromosomes / 46

2. Pseudodiploid (46 chromosome with structural or numeric abnormalities: about 40% of cases;
DI of 1.0)

3. Diploid (46 chromosome: 10-15% of cases; DI of 1.0)

4. Hypodiploid (fewer than 46 chromosome: about 8% of cases; DI less than 1.0).

¥ DI becomes a statistically significative prognostic factor when g 1.16, which corresponds to a

modal number of 53 chromosomes: children with higher ploidy (greater than 50 chromosomes)
have the best prognosis; on the contrary, those in the pseudodiploid category have a relatively
poor prognosis.

This is ALL-L2
1- size difference (heterogenous)
2- N:C is not that high (in high N:C ratio ÒALL-L1Ó, the cytoplasm is barely visible)

How to conÞrm?
Cytochemical staining and immunophenotype