UNIVERSITY OF SANTO TOMAS

FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY

HEMATOLOGICAL MALIGNANCIES

CHARACTERISTICS OF LEUKEMIAS, LYMPHOMAS AND MYELOMAS

LEUKEMIA LYMPHOMA MYELOMA

Overproduction of plasma
Overproduction of Solid malignant tumors of cells in bone marrow with
CHARACTERISTIC
leukocytes the lymph nodes concurrent production of
abnormal protein
Lymphocytes
Myelogenous and
CELL TYPE Reed-Sternberg Cells Plasma Cells
Lymphocytic Lineage
diagnostic of Hodgkin
Confined to organs
intitially but can spill over
Freely trespass Blood-
SITE into the circulating blood Bone Marrow
Brain-Barrier
and present leukemic
blood picture

GENETIC AND IMMUNOLOGICAL FACTORS

 TRANSLOCATIONS
o Most common type of DNA change that can lead to leukemia
o A part of one chromosome breaks off and becomes attached to a different chromosome
o The point at which the break occurs affect nearby genes which can turn on oncogenes or turn off
genes that help a cell to mature
o Examples
 t(1;22) Acute Megakaryoblastic Leukemia (FAB M7)
 t(8;21) Acute Myeloblastic Leukemia with Maturation (FAB M2)
 t(9;11) Acute Monocytic Leukemia (FAB M5)
 t(15;17) Acute Promyelocytic Leukemia (FAB M3)
 t(8;22) Burkitt-Type Lymphocytic Leukemia (FAB L3)
 t(2;8) FAB L3
 t(8;14) Burkitt’s Lymphoma and T-Cell Leukemia/Lymphoma
 t(11;14) Multiple Myeloma and Chronic Lymphocytic Leukemia
 t(10;14) T-Cell Leukemia/Lymphoma
 DELETIONS
o May result in the cell losing a gene that helped keep its growth in check
o Examples
 6q deletion – ALL and and Non-Hodgkin’s Lymphoma
 INVERSIONS
o A part of a chromose gets turned around causing a reversed order which can result in the loss of
genes because of failure to read instructions in protein translation
o Examples
 inv(16) – Acute Myelomonocytic Leukemoa with Eosinophilia (FAB M4Eo)
 inv(3) – in Myelodysplatic Syndrome andl Acute Myeloid Leukemias except M3
(Promyelocytic)
 ADDITION
o Extra chromosome or part of a chromosome is gained
o Lead to many copies of a gene within a cell (problematic if it the are oncogenes)
 ONCOGENES
o Single oncogene in a cell is not sufficient to convert the cell into a full-blown cancer cell
o Examples
 Abl – Chronic Myelogenous Leukemia
 Abelson Murine Leukemia viral oncogene
 Myc – Burkitt’s Lymphoma
 Overexpressed due to t(8;14)
 A transcription factor and controls overexpression of several genes
 MYC familiy of oncogene may be activated by gene rearrangement such as the
t(8;14) or amplification
 Ras – Leukemias
 A normal gene that can be converted into an oncogene via point mutation in
most cases
 When ras transcription is increased an excess of the gene’s protein is in the cell,
and the positive signals for cell division begin to outweigh the negative signals
 BCL-2
 B-Cell Lymphoma Gene 2
 BCL2 prevents apoptosis hence overexpression leads to overexpression of cells
 PROTOONCOGENES
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 UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
o Antecedents of oncogenes
o Central regulators of growth in normal cells
 TUMOR SUPRESSING GENES
o Anti-oncogenes
 CELLULAR FACTORS that induce end-stage differentiation
o B-Interferon
o Tumor Growth Factor
o Tumor Necrosis Factor

HAZARDOUS AGENTS

 OCCUPATIONAL
o Ionizing Radiations – increased incedence of leukemia
o Acute and Chronic forms of Myelogenous Leukemia are most frequently associated with radiation
o Chemicals used in laboratory
o Chemists – risk of cancer involving lymphatic system
o Radiologists – cancer involving bone marrow
o Rubber-industry worker – cancer involving the blood
o Woodworkers – cancer involving the lymphatic system
 ENVIRONMENTAL
o Non-Ionizing Radiations
 CHEMICAL/DRUG
o Benzene – Leukemias and Aplastic Anemia
o Increased risk of AML (higher risk than ALL)
o Platinum-based treatment for ovarian cancer – risk of secondary leukemia
 VIRAL AGENTS
o Epstein-Barr Virus (EBV)
o Human T-Cell Leukemia Virus 1 (HTLV-I)

ACUTE LEUKEMIAS

FAB and WHO CLASSIFICATION

Cytoplasm
CYTOPLASM
FAB NAME NUCLEUS Nucleolus CHROMATIN
Abundance
Color and NOTES
Granule
AML not otherwise
Myeloblastic (min. Fine to Coarse
M0 None catgorized
differentiated)
SCANT
Common in <18 mos
Myeloblastic w/o Round to oval Nucleus
M1 variable M:F 1:1
maturation Single to multiple distinct
Nucleolus Surv : 3.5 mos
azurophillic Middle aged
Myeloblastic granules 40% in > 60 y/o
M2 MODERATE
with/without
With maturation M>F 1.6 : 1
Auer rods Surv 8.5 mos
Promyelocytic
Round to Single to Azurophillic Most aggressive
indented to multiple Granules
Bleeding tendency
M3 Myelocytic lobed cottage- (granules FINE PROMINENT with
loaf may multiple Median age (38)
obscure) auer rods M>F 2:1
Surv 16 mos
Risk of leukostasis
Pharyngitis
Gingival hyperplasia
blue to gray
>50 y/o
M4 Myelomonoblastic MODERATE maybe
granulated Most predom secodary
hema malignancy in MM
Round to indented fold Nucleus M > F 1.4 : 1
Single to Multiple distinct
Nucleolus Risk of leukostasis
M5a – Monoblastic
gray-blue
Variable lacy In young adults (16)
SCANT TO dustlike
M5 Monoblastic or ropy
MODERATE lavender
M<F 0.7 : 1
granules M5b – Monocytic
In mid age (49)
M>F 1.8 : 1
Erythremic myelosis
Single to bizarre
Open DiGuglielmo’s
multinucleated
M6 Erythroblastic multilobed Single to
megaloblastoid ABUNDANT red to blue > 50 y/o
Multiple M>F 1.4 : 1
Distinct Surv 11 months
Single to gray blue Organomegaly in children
SCANT TO
M7 Megakaryoblastic Round to Oval Moderately
MODERATE
with Cytopenia
Vacuolated blobbing CD41 and CD61; -antiMPO

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 UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
Slightly Small blasts
Lymphoblastic Uniformly round Single reticulated; ALLs aret he most common
L1 Scant Blue
(pediatric) small indistinct perinucleolar cancer among children
clumping
Single to Large heterogenous blasts
Lymphoblastic Irregular; several Pale;
L2 Fine Moderate
(adult) Indented indistinct Clefted
large
Two to Coarse with Large blasts
Blue and
L3 Burkitt Type Round to oval five, clear Pominent
vacuolated
basophilic parachromatin
CYTOCHEMICAL STAINING

 SUDAN BLACK B
o Differentiation of Acute Myelogenous Leukemia and Acute Myelomonocytic Leukemia from Acute
Lymphocytic Leukemias
o Binds irreversibly to an undefined granule component in granulocytes eosinophils and monocytes
o Reaction product black granular
o Reagents
 Fixative : 40% Formaldehyde solution’s vapor
 SBB in absolute ethanol
 Phenol Buffer
 May Grunwald Giemsa or Lieshman Stain as Counterstain
o Postive Reactions : Granulocytes – sudanophillic as they mature
 Myeloblasts
 Few small granules in golgi region
 Promyelocyte – increased granulation
 Neutrophilic Myelocytes
 Granules concentrated near nucleus or at the rim of cytoplasm
 Metamyelocytes / bands/ segmenters
 Strongly Positive
 Eosinophils
 Positve at periphery of granules (seen in all stages of its development)
 Clear core of eosinophil granules
 Monocytic cells
 Granules scattered over entire cell
o Basophils exhibit variable reaction (bright red or purple staining)
o Negative Reactions : Lymphocytic Lineage – sudanophobic
 Also erythrocytic lineage and Megakaryocytic-thrombocytic lineage
 MPO negative Neutrophils
o Leukemias + in SBB Cytochemical Reaction (1, 2, 4 , 5)
 M1 and M2
 M2 strongly positive
 Variable
 M4 and M5
o Rare cases of ALL show non-granular smudge positivity not seen with MPO
 MYELOPEROXIDASE STAIN
o for differentiating AML blasts from ALL blasts
o marker for primary granules and auer rods
o PERFORM ONLY ON FRESH SPECIMEN
o Reaction product is brown and granular
o Reagents
 Fixative : Buffered formol acetone
 Hydrogen peroxide
 Hematoxylin as countersaatin
 DAB substrate
 Buffer 7.3 (Sorenson’s Phosphate buffer)
o Positive Reactions : Granulocytes (Promyelocytes and Metamyelocytes strongly reacting)
 Neutrophils except blasts
 Strongly positve
 Monocytes except blasts
 Faint reaction with few granules
 Eosinophils
 Strongly positive granules with large eosinophilic granule that is easily
distinguished from netrophil granules
o Variable : megakaryocytic-thrombocytic cells
o Negative
 Erythrocytic cells
 Plasma cells
 Lymphocytic cells
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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
 Basophils
 Blasts
o Leukemias + in MPO Cytochemical Reaction (1, 2, 4, 5 and 7)
 M1 and M2
 M2 ++
 M4 and M5 variable
 M7 + in unfixed samples
 PERIODIC ACID-SCHIFF
o Also for differentiating AML from ALL
o Useful for supporting diagnosis of DiGuglielmo’s (M6) as it stains erythrocytes of M6
 Erythrocytic lineage does not react on PAS except for erythorcytes of M6
o Oxidizes 1-2 glycol groups to produce a stable dialdehyde which give a red product when
exposed to leucobasic fuchsin (Schiff’s reagent)
o Reagents
 Fixative : Methanol
 Periodic Acid 1%
 Schiff’s Reagent
 Aqueous Hematoxylin as counterstain
o Reaction product is diffused-pink or large-red aggregates
o Postive
 Neutrophils except blast forms
 Megakaryocytes and its blasts in Malignant or Proliferative Disease
 Erythrocytes of Fab M6
o Variable Ractions
 Eosinophils, Basophils
 Granules are negative but cytoplasm may contain faintly PAS + granules
 Monocytes
 Faint pink cytoplasm
 May have granules
 Lymphocytes
 May contain few positive granules
 Thrombocytes
 Intense pink or red
 Megakaryocytes
 Diffuse pink or red with coarse red pigments
 Leukemic Lymphoblasts of L1 OR L2
 Coarse or block-like positivity
o Negative Reactions (blasts may show diffuse reaction ocassionally)
 Erythrocytic Cells
 Myeloblasts
 Monoblasts
o Leukemias + in PAS Cytochemical Reaction
 M5, M6, M7
 M5 ++
 L1 or L2 +/-
 NAPTHOL AS-D CHLOROACETATE ESTERASE (LEDER STAIN)
o Use for identifying cells of the granulocytic series
o Specific Esterase stain
o Reaction Product is bright red
o Confined to cells of neutrophil series and mast cells
o Myeloblasts stain rarely while promyelocytes show strong positivity
o Reagents
 Fixative : Buffered Formol Acetate
 Buffer pH 7.4
 Napthol AS-D Chloroacetate Substrate solution in N,N-Dimethyl-formamide
 Coupling reagent : Hexazotized new fuchsin and Sodium nitrate solution
 Counterstain : Hematoxylin
o Positive Reaction
 Promyelocyte
 Myelocyte
 Metamyelocyte
 Bands and Segmenters
o Leukemias + with NASDCA Cytochemical Reaction
 M2, M6, M7 = +
 M4 is +/-
 ALPHA-NAPTHYL ESTERASE
o Non-specific esterase
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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
o Marker for monocytes, megakaryocytes, and plasma cells
o Reagents
 Fixative : Buffered Formol Acetone
 Phosphate Buffer pH 8.0
 A-napthyl butyrate in acetone
 Coupling reagent : Fast Garnet GBC
 Counterstain : Hematoxylin
o Reaction product is brown and granualr
o Postive
 Monocytes stain strongly
 Stain negative when incubated with sodium fluoride
 Histiocytes
 Erythroblasts
 Megakaryoblasts
o Leukemias + with aNA Cytochemical reaction
 M4, M5, M6, M7
 M4 and M5 ++
 M6 and M7 +++
 Acid-Phosphatase Stain
o Acid Phosphatase is present in all hematopoietic cells and are found in lysosomes
o Stains lymphocytic cells = for ALL
o For diagnosis of T-Cell Leukemia
o Tartrate Resistance
 Indicative of Hairy Cell Leukemia
o Leukemias
 ALL esp L1 and L2
 Negative for AMLs
 Leukocyte Alkaline Phosphatase
o Distinguishes CML from leukemoid reactions and myeloproliferative disorders
o Reagents
 4% Formalin Methanol as fixative
 Substrate is Napthol AS Phosphate
 Tris Buffer pH 9
 Fast blue bb salt for coupling
 Neutral red as counter stain
o Reaction product is blue and granular
o LAP score
 Determined by evaluation of staining intensity (0 to 4+) of 100 neutrophils/bands
 0 = negative, no granules
 1+ = ocassional granules scattered in cytoplasm
 2+ = moderate
 3+ = numerous
 4+ = heavy positivity with numerous coarse granules frequently overlying nucleus
 Normal Lap score ranges from 15 to 130
 < 15 Lap Score
 CML
 PNH
 MDS
 > 130 Lap Score
 Infections
 Growth Factor therapy
 Myeloproliferative disorders other than CML
 Inflammatory disorders
 Pregnancy
 Oral contraceptives
 Stess

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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 

IMMUNOLOGICAL MARKERS

 ACUTE MYELOGENOUS LEUKEMIA

o CD3
o CD13
o CD15
o CD117
o MPO
 MEGAKARYOBLASTIC LEUKEMIA
o CD41
o CD61
 ACUTE LYMPHOCYTIC LEUKEMIA
o T-CELL LINEAGE
 CD2
 CD3
 CD5
 CD7
o B-CELL LINEAGE
 CD10 – positive in major cases of precursor ALL
 CD19 – specific surface marker beginning with pre-B cell
 CD20
 CD22
 CD79a – frequently present in precursor B-ALL
 *CD21 – reacts with B-CLL. B-cell lymphomas, T-CLL, Sezary, AML, and CML in blast
crisis

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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
PROGNOSTIC FACTORS PEDIATRIC ALL

LYMPHOID AND PLASMA CELL NEOPLASMS

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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
 CHRONIC LYMPHOCYTIC LEUKEMIAS
o Most common form of leukemia in adults in western countries
o Rare before age 20; uncommon before age 50
o Now diagnosed more often in younger persons
o M>F 2.1:1
o Highest genetoc predisposition among hematological neoplasms
o Classic CLL : usually a B-cell disorder
 B-CLL is biologically and clinically heterogenous hematological malignancy
 90% are nondividing, arrested at G0/G1
o CD5+, CD19+, CD23+ monoclonal B-Cells
 BCL2 gene
o Molecular Genetics
 Variable Region Genes (IgV)
 70% of CLL cses undergo IgV hypermutation (IgVH)
 Presence of IgVH hypermutation = better survival rate (24 yrs)
 No IgVH is associated with cytogenetic changes that forecast poor clinical
outcome
o 11q22-23 deletion
o 17p deletion
o Trisomy 12
o p53 dysfuntion
 Presence of biologically significant levels of IgVH have chromosomal changes
associated with beign course of the disease
o 13q14 deletion
 Zeta-Chain Associated Protein 70 (ZAP-70)
 Signalling associated molecule
 Differentially expressed in CLL subgroup without IgVH mutaton that has poor
outcome
 Enzyme normally expressed on T-Cells
 Critical for the activation of T cells by antigen
 Inappropriate expression in CLL may alter the action of Syk, a protein tyrosine
kinase found in B-Cells
 Thymidine Kinase
 Serum value correlated to IgVH mutational status and disease progression
 CD38
 Membrane protein that marks cellular activation and maturation
 Has signaling avtivit
 Expression often correlates presence of IgVH mutations
 Independent marker of a patient’s clinical outcone
 CD38+ B-CLL = advanced stage
 Micro-RNA (miRNA)
 Regulate expression of protein coding genes
 May act as oncogene, tumor supressor, or both
 Altered miRNA
o Evasion of apoptosis
 BCL-2
o Self Sufficiency in Growth
 Capability of generating own growth signals
o Stimulation of Angiogenesis and Dissemination
 High degree of tissue neovascularization
o Staging and Prognosis (RAI)
 0 = BM and Blood Lymphocytosis
 I = Lymphocytosis with enlarged nodules
 II = Lymphocytosis with enlarged spleen/liver/both
 III = Lymphocytosis with anemia
 IV = Lymphocytosis with thrombocytopenia

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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 

 B-CELL MALIGANCIES
o Monoclonal B-Cell Lymphocytosis (MLD)
 Preced virtually all cases of CLL/SLL
 High Count MLD resembles Rai stage 0
o B-Cell Prolmphocytic Leukemia
 Rare lymphoid neoplasms with poor prognosis
 Requires more than 55% of circulating lymphoid cells to have a morphology of
prolymphocyte
 Occurs in older adults (age 69)
 B-PLL lymphocyte morphology
 Round nucleus with moderate cytoplasm and a distinct punched-out nucleolus
 CD+
 CD19
 CD20
 CD22
 CD4
 t(8,14) and del 17p
 no t(11;14) – differentiates it from mantle cell lymphoma
 CMYC and TP53 mutation
o Hairy Cell Leukemia
 Uncommon
 Mature B-cell malignancy
 BRAF V600E – genetic lesion
 Affects 30 y/o and above
 M>F
 Morphology
 Fine hair-like irregular cytoplasmic projections
 TRAP +
 Markers
 CD19
 CD20
 CD22
 CD24
 CD25
 Interlukin-2 (Tac)
 Strong Sig
o Hairy Cell Leukemia variant (vHCL)
 More aggressive
 vHCL cells are smaller with a central round nucleus, prominent nucleoli, larger N:C ratio
and basophilic cytoplasm
 poor prognosis
o Non-Hodgkin Lymphomas

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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
 More common in boys
 In children, the four most common are
 Diffuse large B-cell lymphoma
 Burkitt’s lymphoma
 Lymphoblastic lymphoma
 Anaplastic large cell lymphima
 Follicular Lymphoma
 In situ follicular neoplasia (ISFN)
 CD10
 t(14;18)
 BCL-2 overexpression
 Mantle Cell Lymphoma
 In situ mantle cell neoplasia (ISMCN)
 Presence of Cyclin D1+ cells
 Aggressive incurable small B-cell lymphoma
 Classic MCL
o IgVH unmutated
o Express SOX1
o Involve lymph nodes and extranodal sites
 NonNodal MCL
o IgVH mutate SOX1-B-cells
 Markers
o CD19
o CD20
o CD5
o FMC7
o sIg +
 t(11;14) ; cyclin D expression
 Marginal Zone B-Cell Lymphoma
 Indolent/slow-growing NHL B cell lymphoma
 Three Types
o Nodal Marginal Zone Lymphoma monocytoid B-Cell Lymphoma
o Splenic Marginal zone
 Associated with hepC
o Extranodal/MALT Marginal Zone Lymphoma
 Most common form
 Risk factors include infection with H.pylori / C.jejuni / C.psitacci /
B.burgdorferi
o CD19, CD20 + and also possibility of CD43 +
o t(11;18) t(14;18) and t(1;14)
 Lymphoplasmacytic Lymphoma (LPL)
 Small lymphocytes, plasmacytoid lymphovytes, palsma cells, and large
lymphocytes
 Associated with high IgM paraprotein such as in Waldenstrom macroglobulinemia
or type ii cryoglobulinemia
 Diffuse Large B-Cell Lymphoma Not Otherwise Specified (DLBCL-NOS)
 Includes EBV+ LBCL of the elderly
 Markers
o CD5
o CD10
o CD30
o CD138
o BCL-6
 Burkitt’s Lymphoma
 Three types
o Endemic/African
 100% associated with EBV
o Sporadic
o Immunodeficiency Associated
 HIV associated
 CMYC oncogene
 Biopsy : starry sky appearance of noplastic cells
o Sky blue nuclei
o Scattered stars of pale staining macrophages
 TdT negative
 sIg + CD19+, CD10+
 Myc oncogene translocations
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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
o t(8;14) = Ig Heavy Chain site
o t(2;8) = kappa light chain site
o t(8;22) = lambda light chain site
o Plasma Cell Dysrasias
 Multiple Myeloma
 Clonal plasma cell neoplasm
 Abnormal protein production
 Plasma cell disorders associated with MM
o Smoldering MM
o IgM-MGUS
o Non IgM-MGUS
o Light Chain MGUS
o Soloitary Plasmacytoma
o Solitary plasmacytoma with minimal marroe involvement
 Onset 40-70 y/o
 More common in men
 Overexpress CD38
 Serum IgM overproduction
 Tall sharp peaks on desitometer
 Monoclonal IgG
 Bence-Jones Protein
o Light chains
 Therapy
o Daratumumab – anit-CD38 humanized antibody
 Kills CD38 negative bearing plasma cells via ADCC
 Most active monoclonal antibody in clinical trials
o Elotuzumab – humanozed anti SLAMF-7
 Targets surface glycoprotein CS1 on myeloma cell and on NK
cells resulting in activation of the NK cell
 ADCC
o Nivolumab – PD-1 pathway
o Chimeric Antigen Receptor T cells (CAR T-Cells)
 Modify autologous T cells with CARs against CD19 by comining
autologous T cells with anti-CD CAR
 Regulatory T cells (CD4 +) inhibit antitumor immune responses
 Waldenstrom Macroglobulinemia
 Found in older men
 MYD88 L265P mutations
 Monoclonal IgM (19s)
 Pleomorphic B-lineage cells
 CD40 ligand expression (CD154)
o Potent inducer of B-cell expansion
 May have Low factor VII
 Hyperviscosity o blood
 Cryoglobulins can be detected
 Therapy : alkylating agents

 HODGKIN DISEASE
o Reed-Sternberg Cells – arise from a single clone, a common B-cell precursor
 Aneuploidy – characteristic feature
 Gain of chromosomes
 1, 2, 5, 12, and 21
 Structural rearrangements of chrom 1 more frequently observed
 T-CELL and NK CELL MALIGNANCIES
o T-Cell Prolymphocytic Leukemia
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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
 55% of circulating lymphoid cells are prolymphocytes
 More frequently experience lymphadenopathy, hepatomegaly and skin lesions than B-PLL
 Differentiation with B-PLL
 CD3+ , CD53+ very strong, CD7+ very strong
 Inv 14
 Mutations TCL1, MTCP 1, ATM, JAK3, and STAT5b
 Large number of small lymphocytes with scant cytoplasm often with prominent
nucleolus
 Resemblance to sezary cells
 Blebbing of cytoplasm
 First line therapy : alemtuzumab
o Sezary Syndrome and Mycosis fungoides
 Leukemic phase of Cutaneous T cell lymphoma – mycosis fungoides
 T-Stages (degree of skin involvement by patches)
 T1 - < 10% body surface
 T2 - > 10%
 T3 – with tumors
 T4 – erythroderma
 Sezary syndrome : erythroderma > 80%
 Sezary cell : small lymphocyte and has a dark staining clumped nuclear
chromatin pattern (cerebriform)
 CD2 CD3 CD4 CD5
o T-Cell Large Granular Lymphocytic Leukemia
 T-Cell LGL
 Simialr to CLL but is composed of mature T-cells
o Adult T-Cell Leukemia/Lymphoma
 Peripheral T cell neoplasm
 Caused by HTLV-1
 Four subtypes
 Acute
 Chronic
 Lymphomatous
 Smoldering
 Circulating tumor cells in peripheral blood appear as cells with hyperlobated nuclei that
sometimes have clover-leaf shape
 CD4+ CD25+ but lack CD7
 FoxP3 + : characteristic of regulatory cells

MYELOPROLIFERATIVE NEOPLASMS

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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 

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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 

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UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 

lord.wynlor | 15  
 
UNIVERSITY OF SANTO TOMAS
FACULTY OF PHARMACY | DEPARTMENT OF MEDICAL TECHNOLOGY
 
References
Graeter, L. J., In Hertenstein, E. G., In Accurso, C. E., & In Labiner, G. H. (2015). Elsevier's medical laboratory
science examination review.

McKenzie, S. B., Williams, J. L., & Landis-Piwowar, K. (2015). Clinical laboratory hematology.

McPherson, R. A., Pincus, M. R., & Henry, J. B. (2017). Henry's Clinical diagnosis and management by laboratory
methods. St. Louis: Elsevier.

Turgeon, M. L. (2017). Clinical Hematology: Theory & Procedures.

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