This document provides information on chronic myelogenous leukemia (CML). It defines CML as an acquired myeloproliferative neoplasm caused by the presence of the Philadelphia chromosome and BCR-ABL fusion gene in the stem cells. CML typically affects adults aged 40-50 years and presents with excessive myeloid cells in the blood and bone marrow. The disease progresses through chronic, accelerated and blastic phases as the percentage of blasts increases and symptoms worsen over time if left untreated. Diagnosis involves blood tests showing elevated white cells, basophils and blasts as well as bone marrow biopsy demonstrating hypercellularity with myeloid hyperplasia.
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
Chronic myelogenous leukemia (CML) - pluripotential stem cell disease
A malignancy the treatment of which has been revolutionised over the last decade.
Here is a comprehensive discussion on the disease
This presentation is about chronic lymphocytic leukemia (CLL), its epidemiology and incidence, staging, molecular characteristics, clinical features and management.
Learning Objectives:
Introduction
Definition of CML
Philadelphia Chromosome
Normal Granulopoiesis
Pathogenesis of CML
Aetiology
Incidence
Clinical Features
Phases of CML
Lab Diagnosis of CML
Course & Prognosis
Differential Diagnosis
Brief Overview of Treatment
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
Chronic myelogenous leukemia (CML) - pluripotential stem cell disease
A malignancy the treatment of which has been revolutionised over the last decade.
Here is a comprehensive discussion on the disease
This presentation is about chronic lymphocytic leukemia (CLL), its epidemiology and incidence, staging, molecular characteristics, clinical features and management.
Learning Objectives:
Introduction
Definition of CML
Philadelphia Chromosome
Normal Granulopoiesis
Pathogenesis of CML
Aetiology
Incidence
Clinical Features
Phases of CML
Lab Diagnosis of CML
Course & Prognosis
Differential Diagnosis
Brief Overview of Treatment
plastic anemia is a rare bone marrow failure disorder in which the bone marrow stops making enough blood cells (red blood cells, white blood cells, and ...
Disease of older males.
The Philadelphia chromosome - BCR-ABL gene and it’s Tyrosine kinase protein – central to the pathogenesis.
Occurs in 3 phases
Imatinib has revolutionized the management
A myeloprolifrative stem cell disorder resulting in
Proliferation of all haematopoietic lineages but
manifestation Predominantly in the granulocytic series.
The disease occurs chiefly between 30 and 80 years, with
A peak incidence at the 55 years.
*accounts for 20% of all leukaemis.
*found in all races.
*the aetiology is unknown.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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7. Definition
• CML is an acquired clonal myeloproliferative
neoplasm of the abnormal pluripotent
hematopoietic stem cell.
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8. • It is distinguished by other MPN by the presence of
chimeric fusion BCR-ABL gene characteristic
chromosomal abnormality, i.e. Philadelphia (Ph)
chromosome in > 90% cases.
• It is characterized by neoplastic proliferation causing
excessive production and reduced apoptosis of cells
of the myeloid series in the bone marrow.
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9. EPIDEMIOLOGY
• CML is the commonest leukemia constituting
25 – 30 % of all leukaemia in India.
• Sex : Males are affected more than females.
• Age : CML occurs in all age groups, but most
commonly in the middle- aged and elderly
• Adults 40-50 yrs are affected mainly.
• Disease is uncommon in < 20 yrs of age.
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10. • Its annual incidence is 1–2 per 100,000
people,
• CML represents about 15–20% of all cases of
adult leukemia in Western populations.
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11. ETIOLOGY AND PATHOGENESIS
• In majority of the cases the etiology is not
known.
• Exposure to ionizing radiation may increase
the risk and is dose-dependent.
• The evidences which support this risk factor
are……….
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12. • 1. Increased incidence of CML in survivors of
Hiroshima and Nagasaki atomic blasts.
• 2.Patients who have received radiation for
cancer therapy have higher chances of
developing CML compared to normal
individuals
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13. Molecular pathogenesis
• CML is an acquired disease of hematopoietic
stem cell and BCR-ABL fusion gene is
demonstrable in erythroid, myeloid ,
megakaryocytic precursors .
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18. Pathophysiology
Translocation, parts of two chromosomes (the 9th and 22nd)
Part of the BCR("breakpoint cluster region") genefrom
chromosome 22 is fused with the ABLgene on chromosome9.
Thisabnormal "fusion" gene generates aprotein of p210or
sometimes p185
Becauseabl carries adomain that can add phosphate groups to
tyrosine residues (a tyrosine kinase), the bcr-abl fusiongene
product is also atyrosine kinase.
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19. The fused bcr-abl protein interacts with the interleukin 3beta(c)
receptor subunit
Thebcr-abl transcript is continuously active and does not require
activation by other cellular messaging proteins. In turn, bcr-abl
activates acascadeof proteins which control the cell cycle,
speeding up cell division
Bcr-abl protein inhibits DNArepair, causing genomic instabilityand
making the cell more susceptible to developing further genetic
abnormalities.
Theaction ofthe bcr-abl protein is the pathophysiologic causeof
chronic myelogenous leukemia.
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22. PHASES OF CML
• There are 3 phases of CML
• - Chronic phase
• - Accelerated Phase
• - Blastic phase
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23. CHRONIC PHASE
• Chronic CML :
• most of the patients present in this phase.
• It is stable phase, lasts for 2-6 yrs.
• Blasts are usually 2 – 5 % in blood/ marrow.
• It may gradually transform to accelerated
phase or abruptly to Blastic phase.
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31. ACCELEARTATED PHASE
• More aggressive phase.
• Lasts for few months and usually transforms into
blastic phase.
• Blasts are > 10 % , but < 20%.
• Spleen fails to regress with treatment or size starts
increasing.
• Basophils > 20%.
• Hb < 7 g/ dl.
• PLT < 1 lakh or > 10 lakhs /mm3 & unresponsive
therapy.
• NAP score may be increased
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32. BLASTIC PHASE
• Blasts > 20% in blood or BM ( WHO) may be
myeloid type ( 70 % cases ) or type (30% cases).
• Flowcytometry confirms the nature of the blast
crisis.
• Lymphadenopathy may be appear
• Lasts for a few weeks – months
• Granulocytic sarcomas may develop
• Marrow fibrosis may result in marrow failure
• Thrombocytopenia results in bleeding episodes
• Extramedullary blasts proliferation
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40. • 3.immature white cells
• PBS – demonstrates immature white cells of
all stages i.e. neutrophils, metamyelocytes,
myelocytes, promyelocytes and blasts cells .
• There is a predominance of myelocytes in
untreated patients.
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42. • 4.Basophilia and Eosinophilia :
• Basophilia and Eosinophilia are features of
CML .
• Basophils and Eosinophils may be increased to
5 -15 %
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43. • 5. NAP score :
• NAP ( Neutrophil Alkaline Phosphatase ) score
in CML is decreased to (0-20 % ) in more than
90 % cases and is a differentiating features
from leukemoid reactions.
• Normal NAP Score ( 40-100)
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44. • 6.Platelet count :
• Thrombocytosis in the range of 300-500 x
109/L is a feature in CML , however half of
the patients demonstrates normal PLT count.
• Thrombocytopenia in CML is an ominous sign
and suggests an impending accelerated or
blastic phase.
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45. BIOCHEMICAL FINDINGS
• S. uric Acid – increased due to high turnover
of white cells.
• S.LDH – Increased
• S.Alkaline Phosphatase : increased
• Transcobalamine -1 levels - increased
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46. BONE MARROW
• Markedly hypercelular
• There is marked myeloid hyperplasia.
• M:E Ratio : Is markedly increased to 20:1 to
49:1
• Blast cells : are usually 2-5% in chronic phase.
• Basophils & their precursors and Eosinophils
and their precursors are demonstrable.
• Erythroid precursors : decreased.
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47. • Myeloid Hyperplasia
• Megakaryocytes normal / Increased
• Dwarf –megakaryocytes present
• Gaucher like cells ( Large Histiocytes present)
• Marrow fibrosis present.
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