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−==Definition / Description of Disease==
−Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that is characterized by clonal expansion of predominantly granulocytic proliferation (neutrophils, eosinophils and basophils). The majority of the patients with CML are known to have a gene rearrangement called the Philadelphia Chromosome, which is a balanced genetic translocation t(9;22)(q34.1;q11.2) involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. Althought 80% of the clonal evolution in CML cases can be attributed to classic Ph chromosome, secondary cytogenetic aberrations can be seen such as isochromosome 17q, gain of chromosome 8 or 19. ML was first recognized in 1845<ref>{{Cite journal|last=Jm|first=Goldman|last2=Jv|first2=Melo|date=2003|title=Chronic Myeloid Leukemia--Advances in Biology and New Approaches to Treatment|url=https://pubmed.ncbi.nlm.nih.gov/14534339/|language=en|pmid=14534339}}</ref>. Nowell and Hungerford in 1960, who coined the term Philadelphia Chromosome after realizing consistent chromosomal abnormality in leukemic cells.<ref>{{Cite journal|last=Nowell|first=Peter C.|date=2007|title=Discovery of the Philadelphia chromosome: a personal perspective|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934591/|journal=Journal of Clinical Investigation|volume=117|issue=8|pages=2033–2035|doi=10.1172/JCI31771|issn=0021-9738|pmc=1934591|pmid=17671636}}</ref> Later in 1973, the characteristic cytogenetic feature of CML was identified: reciprocal translocation of t(9;22)(q34.1;q11.2).<ref>{{Cite journal|last=Jd|first=Rowley|date=1973|title=Letter: A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia Identified by Quinacrine Fluorescence and Giemsa Staining|url=https://pubmed.ncbi.nlm.nih.gov/4126434/|language=en|pmid=4126434}}</ref> CML has the capacity to expand in both myeloid and lymphoid lineages. However, expansion is predominantly in the granulocyte compartment of the myeloid lineages in the bone marrow.<ref>{{Cite journal|last=S|first=Faderl|last2=M|first2=Talpaz|last3=Z|first3=Estrov|last4=S|first4=O'Brien|last5=R|first5=Kurzrock|last6=Hm|first6=Kantarjian|date=1999|title=The Biology of Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10403855/|language=en|pmid=10403855}}</ref> In the previous WHO 4th edition, CML was be divided into 3 phases of disease: chronic phase, accelerated phase and blastic phase. Currently, in the revised classification of CML, AP at diagnosis or during treatment has been omitted and replaced by recognising only the chronic and blast phases
−==Synonyms / Terminology==
−Formerly chronic myelogenous leukemia or chronic granulocytic leukemia
−==Epidemiology / Prevalence==
−Global annual incidence of CML is 1-2 cases per 100,000 population. CML has male predominance with male to female ratio of 1.4:1. The prevalence of CML is increasing due to successful Tyrosine kinase inhibitor (TKI) therapy. Predilection of CML among certain ethnic groups has not been reported.<ref>{{Cite journal|last=Jv|first=Melo|last2=De|first2=Gordon|last3=Nc|first3=Cross|last4=Jm|first4=Goldman|date=1993|title=The ABL-BCR Fusion Gene Is Expressed in Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/8417787/|language=en|pmid=8417787}}</ref> Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries.<ref>{{Cite journal|last=Am|first=Mendizabal|last2=P|first2=Garcia-Gonzalez|last3=Ph|first3=Levine|date=2013|title=Regional Variations in Age at Diagnosis and Overall Survival Among Patients With Chronic Myeloid Leukemia From Low and Middle Income Countries|url=https://pubmed.ncbi.nlm.nih.gov/23411044/|language=en|pmid=23411044}}</ref> The median age of patients diagnosed with CML is 66 years according to Surveillance, Epidemiology, and End Results (SEER) program and Medical Research Council (MRC) data. Although the etiology of CML is largely unknown, cases of CML have been reported in association with radiation exposure. No studies have shown any genetic inheritance of CML.
−==Clinical Features==
−Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
−{| class="wikitable"
−|'''Signs and Symptoms'''
−|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
−<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
−<span class="blue-text">EXAMPLE:</span> Fatigue
−<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
−|-
−|'''Laboratory Findings'''
−|<span class="blue-text">EXAMPLE:</span> Cytopenias
−<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
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−Approximately 50% of the patients who are diagnosed with CML are asymptomatic and diagnosed during the routine blood tests.<ref name=":0">Silver RT. Molecular Biology of CML. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK13554/</nowiki></ref> CML is a hematological disease that occurs predominantly in adults but in rare cases, it can occur in the pediatric population.<ref>{{Cite journal|last=Am|first=Mendizabal|last2=P|first2=Garcia-Gonzalez|last3=Ph|first3=Levine|date=2013|title=Regional Variations in Age at Diagnosis and Overall Survival Among Patients With Chronic Myeloid Leukemia From Low and Middle Income Countries|url=https://pubmed.ncbi.nlm.nih.gov/23411044/|language=en|pmid=23411044}}</ref> The onset of CML is insidious. Patients with CML usually experience dragging sensation of the abdomen due to splenomegaly. The clinical hallmark of CML is the uncontrolled proliferation of mature and maturing granulocytes at all stages of maturation: metamyelocytes, myelocytes, promyelocytes, and myeloblasts. Patients with CML usually begin with the initial chronic phase before entering the terminal blastic phase and 60-80% of the patients go through accelerated phase before reaching the terminal blastic phase. In chronic phase, CML patients show abnormal routine blood tests with clinical symptoms such as unintentional weight loss, loss of appetite, satiety, fatigue, insomnia and palpable splenomegaly. In rare cases, hyperviscosity syndrome can be a manifestation with a wide spectrum of features such as priapism, tinnitus, hearing loss, cerebral accidents and blindness. In the blastic phase, CML leukemic cells resemble acute leukemic cells morphologically. CNS and lymph node involvement are notable in the blastic phase of CML. If untreated, CML patients will progress to the terminal blastic phase in 3 to 5 years.
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−<center><span style="color:Maroon">'''End of V4 Section'''</span>
−----
−</blockquote>
−==Sites of Involvement==
−Spleen is known to be the most common site of involvement as patients with CML usually present with splenomegaly. Literature has shown that bone marrow is always involved in patients with CML.
−==Morphologic Features==
−[[File:CML 1.jpg|thumb|Chronic Myeloid Leukemia. Image courtesy of Jack Reid, MD]]
−Morphologically, peripheral blood smear shows the classic features of chronic-phase CML: granulocytic leukocytosis with left shift, neutrophilia, no increase in blasts, myelocyte “bulge” and basophilia.<ref>Vardiman JW, et al., (2016). Chronic myeloid leukaemia, BCR-ABL1-positive, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, et al., Editors. IARC Press: Lyon, France, p30-36.</ref> Granulocytes seen in CML patients usually lack dysplastic features. In bone marrow, the aspirate smear shows classic features of CML: marked increase in neutrophils and precursors with a myeloid: erythroid ratio of > 10:1 and small hypolobated megakaryocytes. CML can sometimes present with thrombocytosis in peripheral blood smear, mimicking essential thrombocythemia (ET). Most of the time, primary myelofibrosis (PMF) share overlapping morphological features with CML in the peripheral blood; one distinguishing feature is that the megakaryocyte morphology in PMF is large, bizarre, and hyperchromatic, which is the feature not seen in the CML.
−==Immunophenotype==
−The role of immunohistochemistry is minimal in diagnosing CML. CML usually shows blastic markers (CD 34, CD 117, TdT), which can be useful to confirm extramedullary (splenic involvement with blastic transformation). Lineage-specific markers (MPO, lysosome, CD42b, CD79a, PAX5, CD3) are helpful in distinguishing among myeloid, lymphoid or megakaryocytic transformation.
−{| class="wikitable sortable"
−|-
−!Finding!!Marker
−|-
−|Positive||CD34
−|-
−|Positive||CD117
−|-
−|
−Positive
−|Tdt
'''+
{{DISPLAYTITLE:Chronic myeloid leukaemia}}
{{DISPLAYTITLE:Chronic myeloid leukaemia}}
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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
{{Under Construction}}
{{Under Construction}}
−<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Chronic Myeloid Leukemia (CML), BCR-ABL1 Positive]].
+<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Chronic Myeloid Leukemia (CML), BCR-ABL1 Positive]].
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|Subtype(s)
|Subtype(s)
|Chronic myeloid leukaemia
|Chronic myeloid leukaemia
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CML is the first cancer that is known to be linked to a specific genetic abnormality, namely the balanced chromosomal translocation known as Philadelphia Chromosome. A focal gene area of BCR (Breakpoint Cluster Region) from chromosome 22 is fused with another gene ABL (Tyrosine protein kinase ABL) that is located on chromosome 9. The chimeric oncogene BCR-ABL is the central to the pathology of CML because ABL carries a domain that is capable of phosphorylating tyrosine residues, activating a cascade of proteins that control the cell cycle. It was reported that 90% - 95% of the CML in chronic phase shows characteristic t(9;22)(q34;q11.2) reciprocal translocation that results in the Ph chromosome. This balanced translocation leads to the formation of the ''BCR/ABL'' fusion gene on chromosome 22 and a reciprocal ''ABL/BCR'' fusion gene on chromosome 9. Studies has shown that the latter gene ''ABL/BCR'' fusion gene does not seem to have any crucial role in CML and no ABL/BCR protein has been found.
CML is the first cancer that is known to be linked to a specific genetic abnormality, namely the balanced chromosomal translocation known as Philadelphia Chromosome. A focal gene area of BCR (Breakpoint Cluster Region) from chromosome 22 is fused with another gene ABL (Tyrosine protein kinase ABL) that is located on chromosome 9. The chimeric oncogene BCR-ABL is the central to the pathology of CML because ABL carries a domain that is capable of phosphorylating tyrosine residues, activating a cascade of proteins that control the cell cycle. It was reported that 90% - 95% of the CML in chronic phase shows characteristic t(9;22)(q34;q11.2) reciprocal translocation that results in the Ph chromosome. This balanced translocation leads to the formation of the ''BCR/ABL'' fusion gene on chromosome 22 and a reciprocal ''ABL/BCR'' fusion gene on chromosome 9. Studies has shown that the latter gene ''ABL/BCR'' fusion gene does not seem to have any crucial role in CML and no ABL/BCR protein has been found.
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−<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
+<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
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Not Applicable.
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Atypical chronic myeloid leukemia (aCML) is a subtype of myelodysplastic/myeloproliferative neoplasm that lacks Philadelphia chromosome or rearrangements of PDGFRA, PDGFRB, or FGFR1. This hematological disorder has a considerable overlapping clinicopathological features with CML and CMML. It differs from CML by older median age, lower level of granulocytosis, multilineage dysplasia and lack of basophilia. Up until now, no cytogenetic changes have been associated with aCML. In peripheral blood smear, aCML typically shows granulocytic leukocytosis with striking neutrophil dysplasia (nuclear hyposegmentation and hypogranularity).
Atypical chronic myeloid leukemia (aCML) is a subtype of myelodysplastic/myeloproliferative neoplasm that lacks Philadelphia chromosome or rearrangements of PDGFRA, PDGFRB, or FGFR1. This hematological disorder has a considerable overlapping clinicopathological features with CML and CMML. It differs from CML by older median age, lower level of granulocytosis, multilineage dysplasia and lack of basophilia. Up until now, no cytogenetic changes have been associated with aCML. In peripheral blood smear, aCML typically shows granulocytic leukocytosis with striking neutrophil dysplasia (nuclear hyposegmentation and hypogranularity).
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
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A few genes were noted to be altered during the transformed stages of CML, namely TP53'', RB1, MYC, CDKN2A, NRAS, KRAS, RUNX1, MECOM, TET2, CBL, ASXL1, IDH1'' and ''IDH2''.
A few genes were noted to be altered during the transformed stages of CML, namely TP53'', RB1, MYC, CDKN2A, NRAS, KRAS, RUNX1, MECOM, TET2, CBL, ASXL1, IDH1'' and ''IDH2''.
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[[File:BCR-ABL-ASS1 abnormal double fusions.jpg|thumb|Image courtesy of Fabiola Quintero-Rivera, MD]]
[[File:BCR-ABL-ASS1 abnormal double fusions.jpg|thumb|Image courtesy of Fabiola Quintero-Rivera, MD]]
−Breakpoint Cluster Region protein (BCR) is encoded by ''BCR'' gene, located on chromosome 22. BCR protein has serine/threonine kinase activity.<ref name=":0" /> The protein is also a GTPase-activating protein for p21rac and other kinases.<ref>{{Cite journal|title=BCR BCR activator of RhoGEF and GTPase [Homo sapiens (human)] - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=613}}</ref> BCR protein is involved in the two main pathways: FGFR1 mutant receptor activation and G-protein signaling HRAS regulation pathway.<ref>{{Cite journal|last=Mn|first=Peiris|last2=F|first2=Li|last3=Dj|first3=Donoghue|date=2019|title=BCR: A Promiscuous Fusion Partner in Hematopoietic Disorders|url=https://pubmed.ncbi.nlm.nih.gov/31105873/|language=en|doi=10.18632/oncotarget.26837|pmc=PMC6505627|pmid=31105873}}</ref> BCR-associated genetic rearrangement gives rise to hematological disorders. The ''ABL1'' gene is located on chromosome 9q34.12 and encodes for ABL1 protein, which was discovered to be a tyrosine kinase protein.<ref>{{Cite journal|last=B|first=Chereda|last2=Jv|first2=Melo|date=2015|title=Natural Course and Biology of CML|url=https://pubmed.ncbi.nlm.nih.gov/25814077/|language=en|pmid=25814077}}</ref> Depending on the breakpoint of the ''BCR'' gene, the size of the fusion protein can vary: p190bcr-abl, p210bcr-abl, and p230bcr-abl, leading to three different isoforms.<ref name=":0" /> ''BCR-ABL1'' gene fusion encodes a chimeric protein, which is mostly 210 kDa(P210''BCRABL1'') with constitutive tyrosine-kinase activity, escaping the cytokine regulation and regulatory controls of many intracellular signaling pathways that are associated with proliferation, differentiation and apoptosis.<ref>{{Cite journal|last=Jb|first=Konopka|last2=Sm|first2=Watanabe|last3=On|first3=Witte|date=1984|title=An Alteration of the Human C-Abl Protein in K562 Leukemia Cells Unmasks Associated Tyrosine Kinase Activity|url=https://pubmed.ncbi.nlm.nih.gov/6204766/|language=en|pmid=6204766}}</ref><ref>{{Cite journal|last=R|first=Ren|date=2005|title=Mechanisms of BCR-ABL in the Pathogenesis of Chronic Myelogenous Leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/15719031/|language=en|pmid=15719031}}</ref> Many of the target proteins that are affected by dimerization of constitutive kinase activity of BCR-ABL fusion protein include STAT, RAS, RAF, JUN kinase, MYC, AKT, and other transducers.<ref>{{Cite journal|last=S|first=Faderl|last2=M|first2=Talpaz|last3=Z|first3=Estrov|last4=S|first4=O'Brien|last5=R|first5=Kurzrock|last6=Hm|first6=Kantarjian|date=1999|title=The Biology of Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10403855/|language=en|pmid=10403855}}</ref><ref>{{Cite journal|last=Cl|first=Sawyers|date=1999|title=Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10219069/|language=en|pmid=10219069}}</ref> It was shown that when CML progresses to the blastic crisis phase, a new additional mutation is acquired GSK3beta, which leads to the activation of beta-catenin, preventing myeloid cell lineages to mature.<ref>{{Cite journal|last=Ch|first=Jamieson|last2=Le|first2=Ailles|last3=Sj|first3=Dylla|last4=M|first4=Muijtjens|last5=C|first5=Jones|last6=Jl|first6=Zehnder|last7=J|first7=Gotlib|last8=K|first8=Li|last9=Mg|first9=Manz|date=2004|title=Granulocyte-macrophage Progenitors as Candidate Leukemic Stem Cells in Blast-Crisis CML|url=https://pubmed.ncbi.nlm.nih.gov/15306667/|language=en|pmid=15306667}}</ref><ref>{{Cite journal|last=Ae|first=Abrahamsson|last2=I|first2=Geron|last3=J|first3=Gotlib|last4=Kh|first4=Dao|last5=Cf|first5=Barroga|last6=Ig|first6=Newton|last7=Fj|first7=Giles|last8=J|first8=Durocher|last9=Rs|first9=Creusot|date=2009|title=Glycogen Synthase Kinase 3beta Missplicing Contributes to Leukemia Stem Cell Generation|url=https://pubmed.ncbi.nlm.nih.gov/19237556/|language=en|doi=10.1073/pnas.0900189106|pmc=PMC2646624|pmid=19237556}}</ref>
+Breakpoint Cluster Region protein (BCR) is encoded by ''BCR'' gene, located on chromosome 22. BCR protein has serine/threonine kinase activity.<ref name=":0">Silver RT. Molecular Biology of CML. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK13554/</nowiki></ref> The protein is also a GTPase-activating protein for p21rac and other kinases.<ref>{{Cite journal|title=BCR BCR activator of RhoGEF and GTPase [Homo sapiens (human)] - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=613}}</ref> BCR protein is involved in the two main pathways: FGFR1 mutant receptor activation and G-protein signaling HRAS regulation pathway.<ref>{{Cite journal|last=Mn|first=Peiris|last2=F|first2=Li|last3=Dj|first3=Donoghue|date=2019|title=BCR: A Promiscuous Fusion Partner in Hematopoietic Disorders|url=https://pubmed.ncbi.nlm.nih.gov/31105873/|language=en|doi=10.18632/oncotarget.26837|pmc=PMC6505627|pmid=31105873}}</ref> BCR-associated genetic rearrangement gives rise to hematological disorders. The ''ABL1'' gene is located on chromosome 9q34.12 and encodes for ABL1 protein, which was discovered to be a tyrosine kinase protein.<ref>{{Cite journal|last=B|first=Chereda|last2=Jv|first2=Melo|date=2015|title=Natural Course and Biology of CML|url=https://pubmed.ncbi.nlm.nih.gov/25814077/|language=en|pmid=25814077}}</ref> Depending on the breakpoint of the ''BCR'' gene, the size of the fusion protein can vary: p190bcr-abl, p210bcr-abl, and p230bcr-abl, leading to three different isoforms.<ref name=":0" /> ''BCR-ABL1'' gene fusion encodes a chimeric protein, which is mostly 210 kDa(P210''BCRABL1'') with constitutive tyrosine-kinase activity, escaping the cytokine regulation and regulatory controls of many intracellular signaling pathways that are associated with proliferation, differentiation and apoptosis.<ref>{{Cite journal|last=Jb|first=Konopka|last2=Sm|first2=Watanabe|last3=On|first3=Witte|date=1984|title=An Alteration of the Human C-Abl Protein in K562 Leukemia Cells Unmasks Associated Tyrosine Kinase Activity|url=https://pubmed.ncbi.nlm.nih.gov/6204766/|language=en|pmid=6204766}}</ref><ref>{{Cite journal|last=R|first=Ren|date=2005|title=Mechanisms of BCR-ABL in the Pathogenesis of Chronic Myelogenous Leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/15719031/|language=en|pmid=15719031}}</ref> Many of the target proteins that are affected by dimerization of constitutive kinase activity of BCR-ABL fusion protein include STAT, RAS, RAF, JUN kinase, MYC, AKT, and other transducers.<ref>{{Cite journal|last=S|first=Faderl|last2=M|first2=Talpaz|last3=Z|first3=Estrov|last4=S|first4=O'Brien|last5=R|first5=Kurzrock|last6=Hm|first6=Kantarjian|date=1999|title=The Biology of Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10403855/|language=en|pmid=10403855}}</ref><ref>{{Cite journal|last=Cl|first=Sawyers|date=1999|title=Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10219069/|language=en|pmid=10219069}}</ref> It was shown that when CML progresses to the blastic crisis phase, a new additional mutation is acquired GSK3beta, which leads to the activation of beta-catenin, preventing myeloid cell lineages to mature.<ref>{{Cite journal|last=Ch|first=Jamieson|last2=Le|first2=Ailles|last3=Sj|first3=Dylla|last4=M|first4=Muijtjens|last5=C|first5=Jones|last6=Jl|first6=Zehnder|last7=J|first7=Gotlib|last8=K|first8=Li|last9=Mg|first9=Manz|date=2004|title=Granulocyte-macrophage Progenitors as Candidate Leukemic Stem Cells in Blast-Crisis CML|url=https://pubmed.ncbi.nlm.nih.gov/15306667/|language=en|pmid=15306667}}</ref><ref>{{Cite journal|last=Ae|first=Abrahamsson|last2=I|first2=Geron|last3=J|first3=Gotlib|last4=Kh|first4=Dao|last5=Cf|first5=Barroga|last6=Ig|first6=Newton|last7=Fj|first7=Giles|last8=J|first8=Durocher|last9=Rs|first9=Creusot|date=2009|title=Glycogen Synthase Kinase 3beta Missplicing Contributes to Leukemia Stem Cell Generation|url=https://pubmed.ncbi.nlm.nih.gov/19237556/|language=en|doi=10.1073/pnas.0900189106|pmc=PMC2646624|pmid=19237556}}</ref>
[[File:9;22 image2K Abnormal Karyogram.jpg|thumb|Image courtesy of Fabiola Quintero-Rivera, MD]]
[[File:9;22 image2K Abnormal Karyogram.jpg|thumb|Image courtesy of Fabiola Quintero-Rivera, MD]]
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−<br />
==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Chronic myeloid leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Chronic_myeloid_leukaemia</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Chronic myeloid leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Chronic_myeloid_leukaemia</nowiki>.
−[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases C]]
+[[Category:HAEM5]]
+[[Category:DISEASE]]
+[[Category:Diseases C]]