Dr. Ogechukwu Mbanu's document discusses acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL). It covers the epidemiology, signs and symptoms, pathogenesis, classification, diagnosis, and treatment of these conditions. APL is a subtype of AML characterized by a translocation of chromosomes 15 and 17. It can be treated effectively with all-trans retinoic acid and chemotherapy.
acute leukemia
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acute leukemia
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Newer biomarkers,techniques & their inclusion in 2016 WHO classification for leukaemia/lymphomas increases the responsibility of the pathologists, requiring to develop an integrated multidisciplinary approach for reporting.
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.
generalized anxiety disorder is very common in primary health care settings .patients usually have somatic complaints and they do not attribute these symptoms to anxiety.the doctor needs to have a high index of suspicion to be able help the patients.
Depression is the leading cause of disability world wide and is a major contributor to the overall global burden of diseases .At its worst depression can cause suicide .
There are effective psychological and pharmacological treatments for depression
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
2. 5/21/2020 2
APL AND DIC
CNS INVOLVEMENT
DIFFERENCIAL
DIAGNOSIS
PROGNOSIS
CONCLUSION
RESOURCES
INTRODUCTION
EPDEMIOLOGY OF AML
HEAMATOPOIESIS
RISK FACTORS
CLASSIFICATION
APL
EPIDEMIOLOGY OF APL
SINGS AND SYMPTOMS
PATHOGENESIS
CLINICAL EVALUATION
3. Leukeamias are cancers that involve heamatopoietic cells
“Acute” - leukemia can progress quickly if not treated, and would
probably be fatal in a few months.
“Myeloid” refers to the type of cell this leukemia starts from.
Acute myeloid leukeamia therefore is a disease in which there is
clonal expansion of myeloid precursor cells with reduced capacity to
differentiate
Also known as acute myelocytic leukemia, acute myelogenous
leukemia, and acute non-lymphocytic leukemia
Can metastasize to lymph nodes, liver, spleen, central nervous
system (brain and spinal cord), and testicles.5/21/2020 3
4. Incidence – 2.7 per 100,000
12.6 per 100,000 in those over 65 years
Median age of presentation : 65 years
More prevalent:
Males
European descent
Hispanic/ latino background (promyelocytic leukemia (AML
M3))
5/21/2020 4
9. The prognosis of AML depends on :
the subtype of AML(determined by lab tests),
the patient’s age,
and other lab test
Two of the main systems are used to classify AML into subtypes
The French-American-British (FAB)
World Health Organization(WHO) classification
FAB divided AML into subtypes, M0 through M7 based
type of cell from which the leukemia develops and
how mature the cells are.
The World Health Organization puts into consideration chromosomal
abnormalities5/21/2020 9
10. FAB SUBTYPE NAME
M0 Undifferentiated acute
myeloblastic leukemia
M1 Acute myeloblastic leukemia with
minimal maturation
M2 Acute myeloblastic leukemia with
maturation
M3 Acute promyelocytic leukemia
(APL)
M4 Acute myelomonocytic leukemia
5/21/2020 10
12. Subtypes M0 through M5 all start in immature forms of
white blood cells.
M6 AML starts in very immature forms of red blood
cells,
while M7 AML starts in immature forms of cells that
make platelets.
5/21/2020 12
13. AML WITH CERTAIN GENETIC ABNORMALITIES
AML with a translocation between chromosomes 8 and 21
AML with a translocation or inversion in chromosome 16
AML with a translocation between chromosomes 9 and 11
APL (M3) with a translocation between chromosomes 15 and 17
AML with a translocation between chromosomes 6 and 9
AML with a translocation or inversion in chromosome 3
AML (megakaryoblastic) with a translocation between chromosomes 1
and 22
AML WITH MYELODYSPLASIA-RELATED CHANGES
AML RELATED TO PREVIOUS CHEMOTHERAPY OR RADIATION5/21/2020 13
14. AML NOT OTHERWISE SPECIFIED - AML that don’t fall into one of the
above groups, and is similar to the FAB classification.
AML with minimal differentiation (M0
AML without maturation (M1)
AML with maturation (M2)
Acute myelomonocytic leukemia (M4)
Acute monocytic leukemia (M5)
Acute erythroid leukemia (M6)
Acute megakaryoblastic leukemia (M7)
Acute basophilic leukemia
Acute panmyelosis with fibrosis5/21/2020 14
15. Abnormal accumulation of promyelocytes
Chromosomal translocation involving the retinoic acid
receptor alpha (rarα or rara) gene
Responsive to all-trans retinoic acid (atra; also known as
tretinoin) therapy unlike other AML
1st described in 1957 by french and norwegian physicians
Laboratory evidence of DIC is present in 70% to 90% of
patients at diagnosis or shortly after.
5/21/2020 15
16. Hemorrhagic events contribute 10% to 15% excess
mortality during induction chemotherapy
Morphologically, identified as AML-M3 by FAB
Cytogenetically (WHO), characterized by a balanced
reciprocal translocation abnormality,
t ( 15 ; 17 ) (q22 ; q12 ); PML - RARA.
One of the most treatable forms of leukemia
The 12-yr PFS(progression – free survival) rate , is
estimated to be approximately 70%.5/21/2020 16
17. 10-12% of AML cases
8% - 15% of pediatric AML
median age is approximately 30–40 years
Incidence is higher among Latin Americans or South Europeans
treatment with topoisomerase II inhibitors(eg anthracyclines
and etoposide) can predispose to APL especially in those with
breast cancers
Around 40% of patients with APL also have a chromosomal
abnormality such as trisomy 8 or isochromosome 17
5/21/2020 17
18. DIC
Fever
Infection as a result of low
neutrophils (neutropenia)
Bone tenderness
Anemia
Fatigue
Weakness
Difficulty breathing (dyspnea)
thrombocytopenia leading to:
easy bleeding
Bruising (ecchymosis)
Gingival bleeding
epistaxis
Menorrhagia5/21/2020 18
19. In 95% cases , retinoic acid receptor-alpha (rara) gene on
chromosome 17 is involved in a reciprocal translocation with
the promyelocytic leukemia gene (pml) on chromosome 15,
The translocation is denoted as t(15;17)(q24;q21)
The RAR-receptor is dependent on retinoic acid for regulation
of transcription
The translocation results in fusion of the retinoic acid receptor
(RARA) gene on chromosome 17 with the promyelocytic
leukemia (PML) gene on chromosome 15.
This leads to expression of a hybrid protein with altered
functions5/21/2020 19
20. The fushion protein binds with enhanced affinity to
sites on the cell's DNA, blocking transcription and
differentiation of granulocyte
It does so by enhancing interaction of nuclear co-
repressor (NCOR) molecule and histone deacetylase
(HDAC).
Physiologic quantities of retinoic acid no longer
sufficient to allow for cell differentiation
Despite the above reactions, additional mutations are
required for the development of leukemia5/21/2020 20
22. - Eight other rare gene rearrangements have been
described in APL
In these variants there is fusing RARA to other genes
“variant chromosomal translocations” [e.g., t(11;17),
t(5;17)],
Can be detected in no less than 5% of APL patients
The significance of these non-PML-RARA transcript
variants is that they may sometimes be resistant to all-
trans-retinoic acid (ATRA) and even arsenic trioxide
(ATO).5/21/2020 22
26. History Fatigue ,weakness ,dyspnea, from aneania
Easy bruising or bleeding from
thrombocytopenia
Fever from infection due to leukocytosis
(10% to 30% present with leukocytosis)
Headaches from CNS involvement
Physical
examination
Pallor , petechial , ecchymosis ,bleeding
from the gum , epistasis
,coagulopathy ( DIC) ,
flow murmur from severe aneamia5/21/2020 26
33. Sensitive to All-trans retinoic acid (ATRA; tretinoin), the acid
form of vitamin A unlike the other leukemia's
it targets the oncogenic transcription factor instead of directly
killing the malignant cells
combined with an anthracycline (e.g.daunorubicin,
doxorubicin, idarubicin or mitoxantrone()
Sometimes also with cytarabine (ara-c).
Another option is to give ATRA plus arsenic trioxide (Trisenox).
This is often used in patients who can’t tolerate an
anthracycline drug, but it’s an option for other patients as well.
5/21/2020 33
35. Gemtuzumab ozogamicin, has been used successfully but is associated
with high toxicity
But Less cardiotoxicity than anthracycline-based treatments -
preferable in these patients.
Induction therapy is continued until remission to a maximum of 90 days
ATRA causes retinoic acid syndrome .
dyspnea, fever,
weight gain,
peripheral edema
Pseudotumour Cerebri
these side effects are treated With dexamethasone
5/21/2020 35
36. What drugs are used depends on what was given for
induction
Some of the options include :
An anthracycline along with ATRA for a few cycles
(sometimes different anthracyclines are used in different
cycles)
An anthracycline plus cytarabine for at least 2 cycles
Arsenic trioxide for 2 cycles (over about 2½ months), then
ATRA plus an anthracycline for 2 cycles
ATRA plus arsenic trioxide for several cycles5/21/2020 36
37. After stable remission is induced,patient undergoes 2 years of maintenance
chemotherapy with
methotrexate,
mercaptopurine and
ATRA
Arsenic trioxide is currently being evaluated for treatment of relapsed
/refractory disease.
tamibarotene, is already in use for of relapsed /refractory cases in some parts
of the world..
5/21/2020 37
38. Arsenic Trioxide (ATO) is the standard ttt of relapsed APL,
+/- ATRA
Gemtuzumab ozogamicin (GO) is also an effective agent for
patients with relapsed APL.
Strongly consider CNS-directed treatment with
intrathecal chemotherapy
Remission rates of greater than 90% with AML M3 patient
treated with ATRA and chemotx (eg, anthracyclines
(idarubicin)) with 60-70% disease free survival
Arsenic trioxide in those that relapse – achieves complete
remission in >90%5/21/2020 38
39. The mechanism for APL-induced DIC is not fully understood
Incresed production of cancer procoagulant such as tissue factor
Tissue factor forms a complex with factor VII to activate factors X and
IX.
Activation of the coagulation cascade more blood clots
There is also a state of hyperfibrinolysis due to
Low levels of plasminogen
Alpha – 2- plasmin inhibitor
expression of anexin II a receptor for plasminogen and plasminogen
activating factor on the surface of leukemic promyelocytes over
production of plasmin and fibrinolysis
5/21/2020 39
40. 5/21/2020 40
Defined as Fibrinogen level < 150 mg / dl OR 2 of
the following criteria;
(1) Fibrinogen 150-200 mg / dl.
(2) FDP (D-dimer).
(3) PT 3 sec. Longer than control
It is usually a medical emergency
In 40% of untreated patients ,pulmonary and cerebral
hemorrages can occur
43. It takes 5 – 8 days for coagulopathy to improve with
treatment
Heparin must not be used for prophylaxis in this setting.
In case of life-threatening bleeding, inhibitors of fibrinolysis
should be considered.
Invasive procedures such as central venous catheterization,
lumbar puncture, and bronchoscopy should be avoided
before and during induction remission
5/21/2020 43
45. Treatment
1. Supportive therapy
Platelets
Cryoprecipitate (fibrinogen)
FFP( fresh frozen plasma)
2. Treatment for obvious thrombosis (e.g thrombophlebitis, mural thrombus)
UFH (unfractionated heparin or low molecular weight heparin)
activated protein C
3. Treatment of underlying malignancy
In the case of AML M3 → All-Trans Retinoic Acid (PML-RARα)
Induces differentiation beyond promyelocyte phase
Only with the more common t(15;17) translocation; - t(11;17) and t(5;17)
do not respond to ATRA
5/21/2020 45
46. Occurs in less than 5% of AML patients (highest incidence in
relapsed promyelocytic (M3) variant)
Routine LP is not performed unless symptoms suggestive of
CNS pathology
Common symptoms
headache
mental status changes
CN palsies (commonly CN III or VI)
CSF findings
blast cells
moderate increase in protein and moderate decrease in
glucose5/21/2020 46
47. Treatment
Intrathecal chemotherapy (methotrexate or cytarabine)
+/- whole brain radiotherapy)
addition of radiotherapy depends on response to
intrathecal chemotx and whether there is cranial nerve
involvement
high relapse rate
Commonly administer prophylactic intrathecal chemotx
in relapsed promyelocytic disease
5/21/2020 47
49. Prognosis is generally good relative to other leukemias
early death is comparatively more common usually due
to severe bleeding, often intracranial hemorrhage.
Risk factors for early death due to hemorrhage include
delayed diagnosis,
late treatment initiation, and
high white blood cell count on admission
Relapse rates are low.
5/21/2020 49
50. Acute promyelocytic leukemia(APL) was first identified as a
distinct subtype of acute myeloid leukemia in 1957.
APL is characterized by three features;
- accumulation of abnormal promyelocytes.
- occurrence of fibrinogenopenia and DIC.
- presence of the specific chromosomal translocation
t(15;17)(q22;q21).
Currently it is one of the most treatable forms of acute leukemia
Treatment must begin before the diagnosis is confirmed in
patients with suspected APL, as early treatment is the key for
survival.5/21/2020 50
51. Andreoli et al. Acute Myelogenous Leukemia. Cecil Textbook of Medicine. 2004; 446-447.
Aoki N et el. A comparative double-blind randomized trial of activated protein C and unfractionated
heparin in the treatment of disseminated intravascular coagulation. Int J Hematol. 2002
Jun;75(5):540-7.
Bernard et al. Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An
Evidence Based Review. Journal of Clinical Oncology. Vol 26. June 1 2008.
Bug G et al. Impact of leukapheresis on early death rate in adult acute myeloid leukemia presenting
with hyperleukocytosis. Transfusion. 2007 Oct;47(10):1843-50.
Estey E. Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Patients. Journal of
Clinical Oncology. Vol 25. May 10 2007.
Giles et al. Leuk Lymphoma. 2001 Jun;42(1-2):67-73.
Jabbour EJ, Estery E, Kantarjian HM. Adult Acute Myeloid Leukemia. Mayo Clin Proc. 2006;81:247-
260.
Larson RA. Treatment of Acute Myeloid Leukemia in Younger Adults. Up to Date Online. June 11,
2008.
You tube strong medicine, others.
Lowenberg B, Downing J, Burnett A. Acute Myeloid Leukemia. NEJM. 1999;341:1051-1061.
Randolph T. Acute promyelocytic leukemia (AML M3) – part 1. Clinical Laboratory Science, Spring
2000; 13(2): 98-105.
Schiffer C. Complications of Acute Myeloid Leukemia. Up to Date Online. June 11, 2008.5/21/2020 51
Editor's Notes
XRT – RADIO THERAPY
CHROMOSOMAL TRANSLOCATION IS A CHROMOSOME ABNORMALITY CAUSED BY REARRANGEMENT OF PARTS BETWEEN NONHOMOLOGOUS CHROMOSOMES. A GENE FUSION MAY BE CREATED WHEN THE TRANSLOCATION JOINS TWO OTHERWISE-SEPARATED GENES, IT
IS DETECTED ON CYTOGENETICS OR A KARYOTYPE OF AFFECTED CELLS.
TRANSLOCATIONS CAN BE BALANCED (IN AN EVEN EXCHANGE OF MATERIAL WITH NO GENETIC
INFORMATION EXTRA OR MISSING, AND IDEALLY FULL FUNCTIONALITY) OR UNBALANCED (WHERE THE EXCHANGE OF CHROMOSOME MATERIAL IS UNEQUAL RESULTING IN EXTRA OR MISSING GENES).
RECIPROCAL TRANSLOCATIONS ARE USUALLY AN EXCHANGE OF MATERIAL BETWEEN NON HOMOLOGOUS CHROMOSOMES
CHROMOSOMAL TRANSLOCATIONS OCCURRING IN GAMETOGENESIS, DUE TO ERRORS IN MEIOSIS, RESULTS IN A CHROMOSOMAL ABNORMALITY FEATURED IN ALL CELLS OF THE OFFSPRING, AS IN TRANSLOCATION CARRIERS
TRANSLOCATIONS THAT OCCUR IN CELLULAR DIVISION OF SOMATIC CELLS, DUE TO ERRORS IN MITOSIS ARE KNOWN AS SOMATIC TRANSLOCATIONS.THEY RESULT ININ ABNORMALITIES
FEATURED ONLY IN THE AFFECTED CELL LINE, AS IN CHRONIC MYELOGENOUS LEUKEMIA WITH THE PHILADELPHIA CHROMOSOME TRANSLOCATION
NONRECIPROCAL TRANSLOCATION
NONRECIPROCAL TRANSLOCATION INVOLVES THE TRANSFER OF GENES FROM ONE CHROMOSOME TO ANOTHER NON HOMOLOGOUS CHROMOSOME
CANCER:
SEVERAL FORMS OF CANCER ARE CAUSED BY ACQUIRED TRANSLOCATIONS (AS OPPOSED TO THOSE PRESENT FROM CONCEPTION); THIS HAS BEEN DESCRIBED MAINLY IN LEUKEMIA (ACUTE MYELOGENOUS LEUKEMIA AND CHRONIC MYELOGENOUS LEUKEMIA). TRANSLOCATIONS HAVE ALSO BEEN DESCRIBED IN SOLID MALIGNANCIES SUCH AS
EWING'S SARCOMA
ACUTE PROMYELOCYTIC LEUKEMIA WAS FIRST CHARACTERIZED IN 1957[2][3] BY FRENCH AND NORWEGIAN PHYSICIANS AS A HYPERACUTE FATAL ILLNESS,[WITH A MEDIANSURVIVAL TIME OF LESS THAN A WEEK.[4] TODAY, PROGNOSES HAVE DRASTICALLY IMPROVED; 10-YEAR SURVIVAL RATES ARE ESTIMATED TO BE APPROXIMATELY 77% ACCORDING TO ONE STUDY
PFS RATES DESCRIBE THE PERCENTAGE OF PEOPLE WHO DON’T HAVE NEW TUMOR GROWTH OR CANCER SPREAD DURING OR AFTER TREATMENT . THE RATES INCLUDE THOSE WHOSE DISEASES RESPONDED COMPLETELY OR PARTIALLY TO TREATMENT .THEY ALSO INCLUDE THOSE WHOSE DISEASE IS STABLE
The median age is
approximately 30–40 years,[28]
which is considerably younger
than the other subtypes of AML
q = long arm of chromosome
P = short arm of chromosone
APL, acute promyelocytic leukemia; PML, promyelocytic leukemia; RARα, retinoic acid receptor alpha.
There are numerous variants of the disease. In addition to the prototypical variant that leads to the same PML-RAR fusion transcript, accounting for approximately 6% of variants, there are also different fusion partners for the RARα gene, including PZLF, NPM1, NuMa, and Stat5b. However, the resulting fusion proteins are very rarely seen in APL, accounting for < 2% of cases.[4] The significance of these non-PML-RAR transcript variants is that they may sometimes be resistant to all-trans-retinoic acid (ATRA) and even arsenic trioxide (ATO).
THIS IS NOT A DEFINITE ORDER OF EVENTS .THE ORDER TO FOLLOW IS DEPENDENT ON THE CLINICAL SCENERIO
Gemtuzumab ozogamicin (GO) is also an effective agent for patients with relapsed APL. Although this drug is no longer commercially available
THE DIC IN APL SHOW HYPERFIBRINOLYSIS
THIS HYPERFIBRINOLYSIS IS DUE TO
LEVELS OF PLASMINOGEN
PLASMINOGEN ACTIVATOR
LEVELS OF ALPHA – 2 - PLASMIN INHIBITOR
EXPRESSION OF ANEXIN II A RECEPTOR FOR PLASMINOGEN AND PLASMINOGEN ACTIVATING FACTOR
ANEXIN II IS FOUND ON THE SURFACE OF LEUKAEMIC PROMYELOCYTES
EXPRESSION LEADS TO OVER PRODUCTION OF PLASMIN AND THUS FIBRINOLYSIS