Leukemias are malignant diseases of the bone marrow characterized by the abnormal proliferation of white blood cells. The document discusses the classification, pathogenesis, epidemiology, clinical features, diagnosis and prognosis of various types of leukemias. It describes the key subtypes of acute and chronic leukemias, focusing on chronic myeloid leukemia, which results from a genetic translocation forming the Philadelphia chromosome and the constitutively active BCR-ABL fusion oncogene that drives uncontrolled myeloid cell growth.
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,
I have listed out the LE cells structure and Microscopical examinaton of LE CELLS, Difference between tart cells and le cells, clinical symptoms and diagnostic procedure.
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,
I have listed out the LE cells structure and Microscopical examinaton of LE CELLS, Difference between tart cells and le cells, clinical symptoms and diagnostic procedure.
ACUTE MYELOID LEUKEMIA is a neoplastic disease characterized by
infiltration of the blood,
bone marrow, and
proliferative, clonal undifferentiated cells of the hematopoietic system.
acute leukemia
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A child with ARFID will display a range of physical and behavioural warning signs. Behavioural signs include a sudden refusal to eat, a fear of choking and difficulty eating meals with others. Physical signs include delayed growth and, depending on your child's age, weight loss or failure to gain weight.
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. Leukaemias
Definition
• Leukaemia is a malignant disease of the
haemopoietic tissue,characterized by the
replacement of normal bone marrow elements
with abnormal blood cells.
• Leukaemic cells are frequently present in the
peripheral blood, commonly invade spleen, liver
and lymph nodes and other tissues of the body,
eg testes, brain, meninges and skin
5. Pathogenesis of Acute leukaemia
• Origin of leukaemia at the genetic level appears
to be related to mutations and altered
expression of oncogenes and tumor suppressor
genes
• Oncogenes regulate cell proliferation and
differentiation
• Abnormal oncogene or tumour suppressor gene
expression induced by translocation and genetic
fusion or mutation results in unregulated cellular
proliferation
6. Pathogenesis of Acute leukaemia
• Genetic alteration occurs within a single
abnormal stem cell or progenitor cell in the
marrow.
• Successive generation of cells derived by
mitosis from the original abnormal cell
gives rise to a clonal population, which,
when sufficiently large, causes clinically
apparent disease
7. Pathogenesis of Acute leukaemia
• Acute leukaemia, blasts cells fail to differentiate
normally, further divisions continue, results in
accumulation, replacement of normal cells by
lymphoblasts or myeloblasts – bone marrow
failure
• Clinical condition correlate with total number of
leukaemic cells in the body.
• When 60% or more of total marrow cells –
peripheral blood involvement, liver, spleen and
lymph nodes are infiltrated.
8. Epidemiologic aspects of
leukaemia
• Host factors
1. Heredity
• Appears not to be inherited but increased
predisposition in some individuals.
Family members of leukaemia pts – possible
shared environment
Identical twin –shared placental circulation
(possible in utero exposures)
9. Epidemiologic aspects of
leukaemia
2. Congenital chromosomal abnormalities
Disorders with genetic abnormalities predispose
to acute leukemias :
- Down’s syndrome 10 to 20 fold increase of
acute leukaemia. AML 1 gene identified in
chromosome 21
- Fanconi’s anaemia (AML)
- Ataxia telaniectasia (ALL,NHL)
10. Epidemiologic aspects of
leukaemia
3. Immunodeficiency
• Hereditary immunodeficiency states,
high incidence of lymphoproliferative disorder
4. Chronic marrow dysfunction
MDS, myeloproliferative disorders, aplastic
anaemia,
increased risk of acute leukaemia
transformation
11. Epidemiologic aspects of
leukaemia
• Environmental factors
1. Ionizing radiation
Exposure associated with develoment of acute and chronic leukaemia
Illustrated in populations exposed to nuclear weapons in Hiroshima and
Nagasaki
2. Chemicals and drugs
Benzene – most frequently documented chemical toxin
Alkylating drugs – pts on combined chemoradiotherapy for Hodgkin’s
disease
Chemotherapy – 10 % - 20% of all AML, secondary AML
12. Epidemiologic aspects of
leukaemia
3. Viruses
Human T cell leukaemia/lymphoma virus
Implicated causative agent for adult T cell
leukaemia/lymphoma
Epstein Barr virus linked to African Burkitt
lymphoma – high grade B cell lymphoma
13. Incidence
• Acute leukaemia comprises > 50% of
leukaemia seen in clinical practice
• ALL, common form in children, peak 3-4
yrs falling off by 10 yrs
• AML occurs in all age groups
common type in adults, elderly, only 10
-15% of leukaemia in childhood
14. Incidence
• Chronic leukaemias
• Generally disease of adults
• CLL extremely rare in children, unusual
before 40 yrs
• CML seen at any age, peak incidence 30-
50 yrs, rare in children
• Distinct juvenile variant (jCML) in children
15. Comparison of Acute and Chronic
leukaemia
Acute Chronic
• Age All ages Adults
• Clinical onset sudden insidious
• Course <6 months 2-6 yr
• Leukaemic cells immature mature
• Anaemia mild-severe mild
• Thrombocytopenia mild-severe mild
• TWBC variable increase
• Organomegaly mild prominent
16. Acute leukaemia
• Acute leukaemia is defined as the
presence of >30% blasts in the bone
marrow at clinical presentation.
• Subdivided into two types on the basis of
blasts.
• Acute lymphoblastic leukaemia
• Acute myeloid leukaemia
17. Clinical features of acute leukaemia
Pathogenesis Clinical features
• Bone marrow failure
• Anaemia Fatigue, malaise,pallor
• Thrombocytopenia Bruising, bleeding
• Neutropenia Fever, infection
18. Clinical features of acute leukaemia
Organ infiltration
• Marrow expansion Bone or joint pain
• Spleen Splenomegaly
• Liver Hepatomegaly
• Lymph nodes Lymphadenopathy
• CNS CNS symptoms
• Gums, mouth gum hypertropy,
oral lesions
36. FAB M3 and M 4 /M 5 features
FAB M3
• Bleeding tendency
• DIVC
• Pancytopenia
• FAB M 4 / M 5
• Gum hypertrophy and infitration
• Skin involvement
• CNS disease
• Granulocytic sarcoma – isolated mass of leukaemia
blasts
37. Laboratory and Radiographic Work-up:
• CBC with manual differential
• Uric Acid level
• Clotting studies (PT, PTT, D-dimer, fibrinogen)
• Bone marrow aspirate and biopsy
• Chest xray
• Echocardiogram
38. Diagnosis Of Acute Leukemia
• Demonstrate > 30% blasts in the bone
marrow.
• Diagnosis of acute leukemia is based on
the following:
1.Morphology of the blasts
2.Cytochemistry( MPO,Sudan black- B,NSS,
PAS).
3.Immunophenotyping
4.Cytogenetics
40. • Others
– Lumbar puncture- leukemic cells
– Uric acid, LDH, Calcium – may be raised
– Renal & liver function test- baseline
– X-ray- lytic bone lesion, enlarge mediastinum
(T-ALL)
41. Morphology
• Majority of leukemias at most of the
centers world over are diagnosed by
morphology and cytochemistry
• Blasts cells are large cells with:
a)High N:C ratio
b)Nucleus is large with open chromatin
c)Nucleoli 1- 5
d)Thin rim to moderate amount of cytoplsm
42. Cytochemistry
• Bone marrow smears are stained to
determine specific enzymes or other
proteins produced by cellular organelles.
43. Cytochemistry
ALL AML
Myeloperoxidase _ +, auer rods
Sudan black _ +, auer rods
Periodic acid schiff + + M6
(coarse granular) (fine blocks)
Nonspecific esterase _ + M4,M5
Acid phosphatase + T ALL +M6
(golgi staining) (diffuse)
50. Cytogenetics
• Essential component in newly diagnosed leukaemic
pts
• Major role in diagnosis
• Subclassification
• Selection of appropriate therapy
• Monitering effects of therapy
51. Cytogenetics
Chromosomal abnormalities associated with distinct
types of leukaemia
• t (15;17) unique to APML (FAB M3)
• Inv (16) AMML with abnormal eosinophilia (M4Eo)
• t (9;22) Ph chromosome in CML , ALL
56. Molecular genetics
• Primarily used for confirmation of suspected
chromosomal abnormality not detected by
conventional cytogenetics.
• Monitoring minimal residual disease following
therapy
Hand out – molecular correlation of common chromosomal abnormalities in acute
leukaemia
57. Prognosis in ALL
Good Poor
• WBC Low High > 50,000
• Sex Girls Boys
• Immunophenotype c-ALL B ALL
• Age Child Infants<2 yrs,
adults
• Cytogenetics Normal Ph+, 11q23
or hyperdiploidy
58. Prognosis in ALL
Good Bad
• Time to clear blasts <1 week >1 week
from blood
• Time to remission <4 weeks >4 weeks
• CNS disease at presentation Absent Present
• Minimal residual disease negative at still positive
1-3 months 3-6 months
59. Prognosis in AML
Good Bad
• Cytogenetics t(15:17) delection of chromosome
t(8;21) 5or7
inv (16) 11q23
t(6;9)
• Bone marrow response <5% blasts >20% blasts after
to remission induction after first course first course
• Age < 60 yrs >60 yrs
61. Chronic Myeloid Leukaemia
•Disorder proliferation of haemopoietic stem cells
•Incidence increases with age
– Median age: 40 - 60
– Youngest so far – 12 years old
•Slightly higher incidence in males
– Male-to-female ratio—1.3:1
•Cause
– Unknown
– Slightly increased risk following high dose irradiation: Japanese
atomic bomb survivor
•Median survival: 5 years
62. Melo. Blood. 1996;88:2375.
Pasternak et al. J Cancer Res Clin Oncol. 1998;124:643.
The Ph Chromosome and the bcr-abl Gene: The t(9;22)
Translocation
FUSION PROTEIN WITH CONSTITUTIVE
TYROSINE KINASE ACTIVITY
bcr-abl
bcr
Philadelphia Chromosome
(or 22q-)
Chromosome 9 q+
abl
Chromosome 9
Chromosome 22
63. Pathogenesis
•Translocation of genetic material between chromosom 9 and 22
results in fusion gene: bcr – abl (Philadelphia chromososom)
• BCR-ABL fusion gene (M-BCR) encodes a protein of molecular
weight 210 kDa that has greater tyrosine kinase activity than the
normal ABL gene product.
64. The Ph Chromosome and the bcr-abl Gene: bcr-abl Gene
Structure
p210Bcr-Abl
c-abl1
p185Bcr-Abl2-11
2-11
Chromosome 9
c-bcr
Chromosome 22
2-11
Exon on chromosome 22
Exon on chromosome 9
Introns
CML breakpoints
Melo. Blood. 1996;88:2375.
Pasternak et al. J Cancer Res Clin Oncol. 1998;124:643.
65. Prevalence of the Philadelphia Chromosome in
Leukemias
Faderl et al. Oncology (Huntingt). 1999;13:169.
%ofPh+patients
0
20
40
60
80
100
CML ALL (adult) ALL (pediatric) AML
95
30
5 2
66. Clinical Presentation
• Asymptomatic in ~50% of cases
– Incidental finding of leucocytosis
• Common symptoms
– Fatigue
– Weight loss/anorexia
– Abdominal fullness
• Common signs
– Palpable splenomegaly
• Common laboratory findings
– Abnormal differential WCC
– Leukocytosis
– Thrombocytosis
– Anemia
– Basophilia
67. CML•3 clinical stages
– Chronic phase
– Accelerated phase
– Blastic phase
•40% patient: disease progress from chronic to blastic
phase
•Blast transformation occur: 3 – 5 years
68. Laboratory investigations in CML
• FBC/FBP – anaemia, leucocytosis, immature
granulocytes, basophilia, thrombocytosis, occasional blast
(chronic phase)
•NAP score – low
•LDH – high
•BMAT – Hypercellular marrow with granulocytic
hyperplasia. Blasts not more than 10%.
•Cytogenetic – Philadelphia chromosome
•Molecular analysis – FISH/RT-PCR
69.
70.
71. Hematologic Parameters by Phase of CML
Parameter Chronic Accelerated Blastic
WBC count (/L) High High High
Blasts (%) 1-10 ≥10, < 20 ≥30
Basophils (%) ↑ ≥20 Basophilia
Platelets ↑ or normal ↓ or ↑ ↓
Bone marrow Myeloid hyperplasia Blasts+++
Editor's Notes
A gene that contributes to the production of a cancer. Oncogenes are generally mutated forms of normal cellular genes (proto-oncogenes). A gene capable, when activated, of transforming a cell. Oncogenes are found in the oncogenically activated state in retroviruses and transformed cells and in their normal non-oncogenically activated state in non-transformed cells in which they are called proto-oncogenes.
the fact or condition of being genetically identical, as to a parent, sibling, or other biological source
MRD stands for Minimal Residual Disease. It is a term that simply put means that they detect leukemia cells with a much greater sensitivity than they did in the early days of childhood leukemia treatment. Instead of looking at 100 cells and finding 1 leukemia cell, they can now look at 10,000 cells and find 1 leukemia cell
Globally, CML has an incidence of 1 to 2 cases per 100,000 population and is responsible for 15% to 20% of all adult leukemia. The median age at presentation is 53 years, with a median range of 45 to 55 years.
The incidence of CML increases with age; up to 30% of patients are 60 years of age or older at presentation, which may influence the selection of treatment options in this population. CML is less common in children, with approximately 10% of patients less than 20 years of age.
CML occurs somewhat more frequently in males, with a male-to-female ratio of 1.3:1.
Approximately 50% of patients are asymptomatic at diagnosis, with CML discovered through routine laboratory blood tests.
Eighty-five percent of patients are diagnosed during the chronic phase of disease.
The Ph chromosome is the result of a reciprocal translocation, t(9;22)(q34;q11), between the long arms of chromosomes 9 and 22.
A segment of the abl gene (Abelson mouse leukemia proto-oncogene) on chromosome 9q34 coding for a nonreceptor tyrosine kinase is translocated to the bcr gene (breakpoint cluster region) on chromosome 22q11 to form an abnormal hybrid bcr-abl gene.
The bcr-abl gene is transcribed into a hybrid messenger RNA; the translation product of this RNA is an abnormal fusion protein tyrosine kinase.
The Ph chromosome was first described in 1960 as a shortened chromosome 22 present in myeloid cells from patients with CML. This was the first report of a human cancer associated with a specific genetic abnormality.
Ninety-five percent of patients with CML have the Ph chromosome—hence, this chromosome is the hallmark of CML.
The Ph chromosome can be detected in BM cells in metaphase by standard cytogenetic techniques.
The Ph chromosome is present in all myeloid cell lineages, including erythrocytes, granulocytes, monocytes, and megakaryocytes, as well as some cells of lymphocytic lineage, indicating that malignant transformation to CML originates at the stem cell level.
Irradiated mice that received BM infected with a retrovirus carrying the p210 Bcr-Abl kinase encoded by the Ph chromosome developed hematologic malignancies, including a myoproliferative disease similar to chronic phase CML.
Globally, CML has an incidence of 1 to 2 cases per 100,000 population and is responsible for 15% to 20% of all adult leukemia. The median age at presentation is 53 years, with a median range of 45 to 55 years.
The incidence of CML increases with age; up to 30% of patients are 60 years of age or older at presentation, which may influence the selection of treatment options in this population. CML is less common in children, with approximately 10% of patients less than 20 years of age.
CML occurs somewhat more frequently in males, with a male-to-female ratio of 1.3:1.
Approximately 50% of patients are asymptomatic at diagnosis, with CML discovered through routine laboratory blood tests.
Eighty-five percent of patients are diagnosed during the chronic phase of disease.
The abl gene, which spans exons 2 through 11 on chromosome 9, encodes native tyrosine kinase (145 kDa). Wild-type Abl (or c-Abl) kinase has normal signal transduction activity in a nonmalignant cell.
During the translocation between chromosomes 9 and 22, the breakpoint in the c-abl gene fragment usually occurs 5&apos; to exon 2. In contrast, the breakpoint site on the bcr gene may vary (eg, between exons b1 and b2, b3, or b4), resulting in fusion gene products of varying lengths, which in turn code for fusion protein tyrosine kinases of different molecular masses: 185/190 kDa, 210 kDa, and 230 kDa (not shown), all with tyrosine kinase activity.
The Bcr portion of the protein interferes with the regulatory component of the c-Abl kinase activity, resulting in kinase activity that is constitutively activated.
The p210Bcr-Abl fusion protein tyrosine kinase is expressed primarily in CML, the p190Bcr-Abl primarily in Ph+ ALL, and the p230Bcr-Abl in a subset of patients with CML.
The Ph chromosome is also seen in leukemias other than CML. About 5% of childhood ALL, 15% to 30% of adult ALL, and 2% of cases of AML are Ph+.
In some patients with CML, the Ph chromosome may not be detectable by cytogenetic analysis. For those cases, molecular techniques such as Southern blotting, fluorescence in situ hybridization (FISH), and reverse transcriptase polymerase chain reaction (RT-PCR) can be used to detect the presence of the bcr-abl gene.
The most common symptoms at presentation in the chronic phase of CML include fatigue, weight loss, abdominal fullness, and night sweats. In 50% of cases, the clinical presentation is asymptomatic.
Physical examination shows palpable splenomegaly in more than 50% of patients.
Typical laboratory results include leukocytosis with an abnormal differential, anemia, basophilia, and thrombocytosis.
CML is a clonal proliferation of a malignant hematopoietic progenitor cell. The disease has been studied extensively and is characterized by defined clinical stages and prognostic factors. The efficacy and safety outcomes from a number of treatment regimens are well documented.
In 1961, an aberrant chromosome that is unique to this disease was identified in bone marrow (BM) cells from patients with CML. Termed the Philadelphia (Ph) chromosome, it is a shortened chromosome 22 resulting from a reciprocal translocation, t(9;22)(q34;q11), between the long arms of chromosomes 9 and 22.
The Ph chromosome, which is present in 95% of patients with CML, produces an abnormal, constitutively activated Bcr-Abl tyrosine kinase that is linked to malignant transformation. Thus, the Bcr-Abl kinase is an attractive target for rational drug design.
CML is a clonal proliferation of a malignant hematopoietic progenitor cell. The disease has been studied extensively and is characterized by defined clinical stages and prognostic factors. The efficacy and safety outcomes from a number of treatment regimens are well documented.
In 1961, an aberrant chromosome that is unique to this disease was identified in bone marrow (BM) cells from patients with CML. Termed the Philadelphia (Ph) chromosome, it is a shortened chromosome 22 resulting from a reciprocal translocation, t(9;22)(q34;q11), between the long arms of chromosomes 9 and 22.
The Ph chromosome, which is present in 95% of patients with CML, produces an abnormal, constitutively activated Bcr-Abl tyrosine kinase that is linked to malignant transformation. Thus, the Bcr-Abl kinase is an attractive target for rational drug design.
Diagnostic tests are critical for confirming the presence of CML and staging the disease to determine potential treatment options.
In a peripheral complete blood count with differential, the white blood cell (WBC) count is typically 20×109/L and may increase as the disease progresses. Increased numbers of granulocytes at all stages of maturation account for many of the elevated WBC counts.
The increase in peripheral blast counts is characteristic as the disease enters the accelerated phase and blastic phase, at which time the disease resembles acute leukemia.
Although elevated platelets are frequently seen in the chronic phase, thrombocytopenia may signal the onset of advanced disease.
Progressive anemia and basophilia are also characteristic of the advanced stages of CML, although lymphocyte and monocyte counts may remain relatively normal.
In BM aspirates and biopsy samples, the marrow is hypercellular with excessive myeloid hyperplasia and a shift to more immature myeloid forms and blasts; the myeloid-to-erythroid ratio is elevated to 10:1 to 30:1 (normal, 2:1 to 5:1).
Eosinophils, basophils, and megakaryocytes are increased in number and may appear dysplastic.
Cytogenetic analysis shows the presence of the Ph chromosome in 95% of patients; however, with advanced disease, additional karyotypic abnormalities may develop.The detection of bcr-abl RNA transcripts by the sensitive polymerase chain reaction is also used.