FACTOID # 11: Oklahoma has the highest rate of women in State or Federal correctional facilities.
 
 Home   Encyclopedia   Statistics   States A-Z   Flags   Maps   FAQ   About 
   
 
WHAT'S NEW
 

SEARCH ALL

FACTS & STATISTICS    Advanced view

Search encyclopedia, statistics and forums:

 

 

(* = Graphable)

 

 


Encyclopedia > Chronic myelogenous leukemia
Chronic myelogenous leukemia
Classifications and external resources
The Philadelphia chromosome as seen by metaphase FISH.
ICD-10 C92.1
ICD-9 205.1
ICD-O: M9863/3
DiseasesDB 2659
MedlinePlus 000570
eMedicine med/371 

Chronic myelogenous leukemia (CML) is a form of chronic leukemia characterized by increased and unregulated clonal production of predominantly myeloid cells in the bone marrow. CML is a myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome. Historically, it has been treated with chemotherapy, interferon and bone marrow transplantation, although targeted therapies introduced at the beginning of the 21st century have radically changed the management of CML. FISH image of bcr/abl positive rearranged metaphase File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ... FISH (Fluorescent in situ hybridization) is a cytogenetic technique which can be used to detect and localize DNA sequences on chromosomes. ... The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The Diseases Database is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Leukemia (or leukaemia; see spelling differences) is a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, usually white blood cells (leukocytes). ... Myeloid cells is a subsummating term for all hemopoietic cells except the lymphoid ones (T-cells, B-cells, NK-cells, dendritic cells). ... Grays Anatomy illustration of cells in bone marrow. ... The myeloproliferative diseases are a group of diseases of the bone marrow where excess cells are produced. ... Chromosomal translocation of the 4th and 20th chromosome. ... Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ... Chemotherapy is the use of chemical substances to treat disease. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Bone marrow transplantation is a medical procedure that involves stem cell transplantation. ... Targeted cancer therapy is a type of chemotherapy which blocks the growth of cancer cells by interfering specific targeted molecules needed for carcinogenesis and tumor growth. ... The 21st century is the present century of the Gregorian calendar. ...

Contents

Incidence and epidemiology

CML occurs in all age groups, but most commonly in the middle-aged and children. Its annual incidence is 1 to 2 per 100,000 people, and slightly more men than women are affected. CML represents about 15-20% of all cases of adult leukemia in Western populations.[1] The only well-described risk factor for CML is exposure to ionizing radiation; for example, increased rates of CML were seen in people exposed to the atomic bombings of Hiroshima and Nagasaki.[2] Ionizing radiation has many practical uses, but it is also dangerous to human health. ... The Fat Man mushroom cloud resulting from the nuclear explosion over Nagasaki rises 18 km (11 mi, 60,000 ft) into the air from the hypocenter. ...


Signs and symptoms

Patients are often asymptomatic at diagnosis, presenting incidentally with an elevated white blood cell count on a routine laboratory test. In this setting, CML must be distinguished from a leukemoid reaction, which can have a similar appearance on a blood smear. Symptoms of CML may include: malaise, low-grade fever, increased susceptibility to infections, anemia, and thrombocytopenia with easy bruising (although an increased platelet count (thrombocytosis) may also occur in CML). Splenomegaly may also be seen. In medicine, a disease is asymptomatic when it is at a stage where the patient does not experience symptoms. ... To meet Wikipedias quality standards, this article may require cleanup. ... The term leukemoid reaction describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). ... Malaise is a term used to refer to a general state of discomfort, tiredness, or illness. ... In medicine, low-grade fever is a continuous or fluctuating low fever, typically defined as never exceeding 38. ... An infection is the detrimental colonization of a host organism by a foreign species. ... This article discusses the medical condition. ... Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... A bruise or contusion or ecchymoses is a kind of injury, usually caused by blunt impact, in which the capillaries are damaged, allowing blood to seep into the surrounding tissue. ... A 250 ml bag of newly collected platelets. ... Thrombocytosis - Wikipedia, the free encyclopedia /**/ @import /skins-1. ... Splenomegaly is an enlargement of the spleen. ...


Pathophysiology

Schematic of the 9;22 translocation resulting in bcr-abl fusion
Schematic of the 9;22 translocation resulting in bcr-abl fusion

CML was the first malignancy to be linked to a clear genetic abnormality, the chromosomal translocation known as the Philadelphia chromosome. This chromosomal abnormality is so named because it was first discovered and described in 1960 by two scientists from Philadelphia, Pennsylvania: Peter Nowell of the University of Pennsylvania and David Hungerford of the Fox Chase Cancer Center. Made by me for an essay File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... Chromosomal translocation of the 4th and 20th chromosome. ... Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ... Nickname: City of Brotherly Love, Philly, the Quaker City Motto: Philadelphia maneto (Let brotherly love continue) Location in Pennsylvania Coordinates: Country United States State Pennsylvania County Philadelphia Founded October 27, 1682 Incorporated October 25, 1701 Mayor John F. Street (D) Area    - City 369. ... The University of Pennsylvania (or Penn[3][4]) is a private, nonsectarian research university located in Philadelphia, Pennsylvania. ... The Fox Chase Cancer Center, is a Research center and hospital located in The Northeast section of Philadelphia, Pennsylvania, United States. ...


In this translocation, parts of two chromosomes (the 9th and 22nd by conventional karyotypic numbering) switch places. As a result, part of the BCR ("breakpoint cluster region") gene from chromosome 22 is fused with the ABL gene on chromosome 9. This abnormal "fusion" gene generates a protein of p210 or sometimes p185 weight (p is a weight measure of cellular proteins in kDa). Because abl carries a domain that can add phosphate groups to tyrosine residues (a tyrosine kinase), the bcr-abl fusion gene product is also a tyrosine kinase. Karyogram of human male using Giemsa staining. ... Possible meanings: Kachin Defense Army Kentucky Distillers Association Kongsberg Defence & Aerospace This page expands a three-character combination which might be any or all of: an abbreviation, an acronym, an initialism, a word in English, or a word in another language. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ...


The fused bcr-abl protein interacts with the interleukin 3beta(c) receptor subunit. The bcr-abl transcript is continuously active and does not require activation by other cellular messaging proteins. In turn, bcr-abl activates a cascade of proteins which control the cell cycle, speeding up cell division. Moreover, the bcr-abl protein inhibits DNA repair, causing genomic instability and making the cell more susceptible to developing further genetic abnormalities. The cell cycle, or cell-division cycle (CDC), is the series of events in a eukaryotic cell between one cell division and the next. ...


The action of the bcr-abl protein is the pathophysiologic cause of chronic myelogenous leukemia. With improved understanding of the nature of the bcr-abl protein and its action as a tyrosine kinase, targeted therapies have been developed (the first of which was imatinib mesylate) which specifically inhibit the activity of the bcr-abl protein. These tyrosine kinase inhibitors can induce complete remissions in CML, confirming the central importance of bcr-abl as the cause of CML. Targeted cancer therapy is a type of chemotherapy which blocks the growth of cancer cells by interfering specific targeted molecules needed for carcinogenesis and tumor growth. ... Imatinib mesylate (or simply imatinib) is a new drug used to treat certain types of cancer. ...


Diagnosis

CML is often suspected on the basis on the complete blood count, which shows increased granulocytes of all types. Basophils and eosinophils are almost universally increased; this feature may help differentiate CML from a leukemoid reaction. A bone marrow biopsy is often performed as part of the evaluation for CML, but bone marrow morphology alone is insufficient to diagnose CML. Schematics of shorthand for complete blood count commonly used by physicians. ... Granulocytes are a category of white blood cells characterised by the presence of granules in their cytoplasm. ... Categories: Wikipedia cleanup | Biology stubs | Blood and immune system cells ... Eosinophils are white blood cells that are responsible for combating infection by parasites in the body. ... The term leukemoid reaction describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). ... A bone marrow biopsy is a medical procedure used as part of a test in the diagnosis of several conditions including leukemia. ...


Ultimately, CML is diagnosed by detecting the Philadelphia chromosome. This characteristic chromosomal abnormality can be detected by routine cytogenetics, by fluorescent in situ hybridization, or by PCR for the bcr-abl fusion gene. Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ... A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ... FISH (Fluorescent in situ hybridization) is a cytogenetic technique which can be used to detect and localize DNA sequences on chromosomes. ... Wikipedia does not yet have an article with this exact name. ...


Controversy exists over so-called Ph-negative CML, or cases of suspected CML in which the Philadelphia chromosome cannot be detected. Many such patients in fact have complex chromosomal abnormalities which mask the (9;22) translocation, or have evidence of the translocation by FISH or RT-PCR in spite of normal routine karyotyping.[3] The small subset of patients without detectable molecular evidence of bcr-abl fusion may be better classified as having an undifferentiated myelodysplastic/myeloproliferative disorder, as their clinical course tends to be different from patients with CML.[4] FISH (Fluorescent in situ hybridization) is a cytogenetic technique which can be used to detect and localize DNA sequences on chromosomes. ... RT-PCR (Reverse Transcription-PCR) is a modification of PCR in which an RNA strand is first reverse transcribed into its DNA complement or cDNA, followed by amplification of the resulting DNA using PCR. This can either be a 1 or 2 step process. ...


Phases of CML

CML is often divided into three phases based on clinical characteristics and laboratory findings. In the absence of intervention, CML typically begins in the chronic phase, and over the course of several years progresses to an accelerated phase and ultimately to a blast crisis. Blast crisis is the terminal phase of CML and clinically behaves like an acute leukemia. One of the drivers of the progression from chronic phase through acceleration and blast crisis is the acquisition of new chromosomal abnormalities (in addition to the Philadelphia chromosome).[1] Some patients may already be in the accelerated phase or blast crisis by the time they are diagnosed. Acute leukemia may refer to: Acute myelogenous leukemia Acute lymphocytic leukemia Blast crisis of chronic myelogenous leukemia This is a disambiguation page — a navigational aid which lists other pages that might otherwise share the same title. ...


Chronic phase

Approximately 85% of patients with CML are in the chronic phase at the time of diagnosis. During this phase, patients are usually asymptomatic or have only mild symptoms of fatigue or abdominal fullness. The duration of chronic phase is variable and depends on how early the disease was diagnosed as well as the therapies used. Ultimately, in the absence of curative treatment, the disease progresses to an accelerated phase.


Accelerated phase

Criteria for diagnosing transition into the accelerated phase are somewhat variable; the most widely used criteria are those put forward by investigators at M.D. Anderson Cancer Center,[5] by Sokal et al,[6] and the World Health Organization.[7] The WHO criteria are perhaps most widely used, and include: M. D. Anderson Cancer Center was created by the Texas Legislature in 1941 as a component of the University of Texas System, and the faculty numbers 1,069 both M.D.s and Ph. ... Flag of World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations, acting as a coordinating authority on international public health, headquartered in Geneva, Switzerland. ...

  • 10-19% myeloblasts in the blood or bone marrow
  • >20% basophils in the blood or bone marrow
  • Platelet count <100,000, unrelated to therapy
  • Platelet count >1,000,000, unresponsive to therapy
  • Cytogenetic evolution with new abnormalities in addition to the Philadelphia chromosome
  • Increasing splenomegaly or white blood cell count, unresponsive to therapy

The patient is considered to be in the accelerated phase if any of the above are present. The accelerated phase is significant because it signals that the disease is progressing and transformation to blast crisis is imminent. Myeloblasts or blasts are new, immature blood cells developed in the bone marrow that are the precursors of myelocytes. ... Grays Anatomy illustration of cells in bone marrow. ... Categories: Wikipedia cleanup | Biology stubs | Blood and immune system cells ... A 250 ml bag of newly collected platelets. ... Splenomegaly is an enlargement of the spleen. ...


Blast crisis

Blast crisis is the final phase in the evolution of CML, and behaves like an acute leukemia, with rapid progression and short survival. Blast crisis is diagnosed if any of the following are present in a patient with CML: Acute leukemia may refer to: Acute myelogenous leukemia Acute lymphocytic leukemia Blast crisis of chronic myelogenous leukemia This is a disambiguation page &#8212; a navigational aid which lists other pages that might otherwise share the same title. ...

  • >20% myeloblasts or lymphoblasts in the blood or bone marrow
  • Large clusters of blasts in the bone marrow on biopsy
  • Development of a chloroma (solid focus of leukemia outside the bone marrow)

Myeloblasts or blasts are new, immature blood cells developed in the bone marrow that are the precursors of myelocytes. ... Lymphoblasts are interferons produced predominantly by leucocyte cells. ... A bone marrow biopsy is a medical procedure used as part of a test in the diagnosis of several conditions including leukemia. ... A chloroma is a solid tumor composed of immature white blood cells called myeloid precursor cells. ...

Treatment

Chronic phase

Chronic phase CML is treated with imatinib mesylate (marketed as Gleevec® or Glivec®; previously known as STI-571). In the past, antimetabolites (e.g. cytarabine, hydroxyurea), alkylating agents, interferon alfa 2b, and steroids were used, but this has been replaced by imatinib. Imatinib is a new agent, approved by the US FDA in 2001, which specifically targets BCR/abl, the constitutively activated tyrosine kinase fusion protein caused by the Philadelphia chromosome translocation that is felt to be responsible for driving the abnormal cell proliferation in of CML. It is better tolerated and more effective than previous therapies. Bone marrow transplantation was also used as initial treatment for CML in younger patients before the advent of imatinib, and while it can often be curative, there is a high rate of transplant-related mortality. Imatinib is a drug used to treat certain types of cancer. ... Cytarabine is a shortened form of cytosine arabinoside, a commonly used chemotherapy agent used mainly in the treatment of leukemia and non-Hodgkin lymphoma. ... Hydroxyurea chemical structure Hydroxyurea or hydroxycarbamide (rINN), (brand names include Hydrea®) is an antineoplastic drug used in hematological malignancies. ... Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Steroid skeleton. ... Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ... Bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ...


Another new drug, dasatinib (marketed as Sprycel®; previously known as BMS-354825), which has a similar mechanism of action to imatinib but inhibiting a broader spectrum of tyrosine kinases, was approved by the U.S. FDA in June 2006 for use in patients with CML who are no longer responding to, or who can no longer tolerate, therapy with imatinib. [1] Dasatinib is a drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel®. Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). ... Imatinib is a drug used to treat certain types of cancer. ...


Various combinations of the different treatment modalities are being explored.


In 2005 favourable results of vaccination were reported with the BCR/abl p210 fusion protein in patients with stable disease, with GM-CSF as an adjuvant.[8] Vaccination is the process of administering weakened or dead pathogens to a healthy person or animal, with the intent of conferring immunity against a targeted form of a related disease agent. ... Granulocyte-Colony Stimulating Factor (G-CSF) is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes. ...


Two other drugs, ceflatonin (homoharringtonine) and nilotinib (AMN 107) are currently in active clinical trials in patients with CML who have developed resistance to imatinib. [2][3] There are very few or no other articles that link to this one. ...


Blast crisis

Blast crisis carries all the symptoms and characteristics of either acute myelogenous leukemia or acute lymphoblastic leukemia, and has a very high mortality rate. This stage can most effectively be treated by a bone marrow transplant after high-dose chemotherapy. In young patients in the accelerated phase, a transplant may also be an option. However the likelihood of relapse after a bone marrow transplant is higher in patients in blast crisis or in the accelerated phase as compared to patients in the chronic phase. Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of blood cells. ... Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a cancer of the white blood cells, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (referred to as lymphoblasts) in the bone marrow. ... Bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ... Chemotherapy is the use of chemical substances to treat disease. ...


Prognosis

The prognosis of CML depends on a number of different parameters. Two different scoring systems are in use: one by Sokal et al (1984) and one by Hasford et al (1998).[9][10]


See also

The term leukemoid reaction describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). ... Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML) and involves an exchange of material between chromosomes 9 and 22. ... The myeloproliferative diseases (MPDs) are a group of diseases of the bone marrow where excess cells are produced. ...

References

  1. ^ a b The biology of chronic myeloid leukemia. Faderl S; Talpaz M; Estrov Z; O'Brien S; Kurzrock R; Kantarjian HM. N Engl J Med 1999 Jul 15;341(3):164-72.
  2. ^ Radiogenic leukemia revisited. Moloney WC. Blood 1987 Oct;70(4):905-8.
  3. ^ Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period. Savage DG; Szydlo RM; Goldman JM. Br J Haematol 1997 Jan;96(1):111-6.
  4. ^ The World Health Organization (WHO) classification of the myeloid neoplasms. Vardiman JW; Harris NL; Brunning RD. Blood 2002 Oct 1;100(7):2292-302.
  5. ^ Kantarjian H, Dixon D, Keating M, Talpaz M, Walters R, McCredie K, Freireich E (1988). "Characteristics of accelerated disease in chronic myelogenous leukemia.". Cancer 61 (7): 1441-6. PMID 3162181.
  6. ^ Sokal J, Baccarani M, Russo D, Tura S (1988). "Staging and prognosis in chronic myelogenous leukemia.". Semin Hematol 25 (1): 49-61. PMID 3279515.
  7. ^ Vardiman J, Harris N, Brunning R (2002). "The World Health Organization (WHO) classification of the myeloid neoplasms.". Blood 100 (7): 2292-302. PMID 12239137.Full text
  8. ^ Bocchia M, Gentili S, Abruzzese E, Fanelli A, Iuliano F, Tabilio A, Amabile M, Forconi F, Gozzetti A, Raspadori D, Amadori S, Lauria F. Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial. Lancet 2005;365:657-62.
  9. ^ Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in good risk chronic granulocytic leukemia. Blood 1984;63:789-799. PMID 6584184.
  10. ^ Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, Alimena G, Steegmann JL, Ansari H. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst 1998;90:850-858. PMID 9625174.

The Lancet is one of the oldest and most respected peer-reviewed medical journals in the world, published weekly by Elsevier, part of Reed Elsevier. ...

External links

 v  d  e 
Health science - Medicine - Hematology
Hematological malignancy and White blood cells
Lymphoid: Lymphocytic leukemia (ALLCLL) | Lymphoma (Hodgkin's disease, NHL) | LPD | Myeloma (Multiple myelomaExtramedullary plasmacytoma)
Myeloid: Myelogenous leukemia (AMLCML) | MPD (Essential thrombocytosisPolycythemia) | MDS | Myelofibrosis | Neutropenia
Red blood cells
Anemia | Hemochromatosis | Sickle-cell disease | Thalassemia | Hemolysis | Aplastic anemia | G6PD Deficiency | Hereditary spherocytosis | Hereditary elliptocytosis | Other hemoglobinopathies
Coagulation and Platelets
Thrombosis | Deep vein thrombosis | Pulmonary embolism | Hemophilia | ITP | TTP | DIC

  Results from FactBites:
 
Chronic myelogenous leukemia - Wikipedia, the free encyclopedia (1599 words)
CML is a myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome.
CML was the first malignancy to be linked to a clear genetic abnormality, the chromosomal translocation known as the Philadelphia chromosome.
CML is often suspected on the basis on the complete blood count, which shows increased granulocytes of all types.
  More results at FactBites »

 
 

COMMENTARY     


Share your thoughts, questions and commentary here
Your name
Your comments

Want to know more?
Search encyclopedia, statistics and forums:

 


Press Releases |  Feeds | Contact
The Wikipedia article included on this page is licensed under the GFDL.
Images may be subject to relevant owners' copyright.
All other elements are (c) copyright NationMaster.com 2003-5. All Rights Reserved.
Usage implies agreement with terms, 1022, m