Changes

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<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-30. The original page can be found at [[HAEM4:Atypical Chronic Myeloid Leukemia (aCML), BCR-ABL1 Negative]].

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-04. The original page can be found at [[HAEM4:Atypical Chronic Myeloid Leukemia (aCML), BCR-ABL1 Negative]].

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==Primary Author(s)*==

==Primary Author(s)*==

==Cancer Sub-Classification / Subtype==

==Cancer Sub-Classification / Subtype==

[[Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)|Myelodysplastic/Myeloproliferative Neoplasm]]

[[HAEM4:Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)|Myelodysplastic/Myeloproliferative Neoplasm]]

==Definition / Description of Disease==

==Definition / Description of Disease==

Atypical chronic myeloid leukemia, ''BCR-ABL1''-negative (aCML) presents with myelodysplastic as well as myeloproliferative features at the time of disease onset<ref name=":5" /><ref>Czader, M and Orazi, A. Chapter 45. Myelodysplastic/Myeloproliferative Neoplasms and Related Diseases. In Orazi A, Foucar K, Knowles DM. eds. Knowles Neoplastic Hematopathology. Riverwoods, IL: Wolters Kluwer Health; 2013:1148-1150.</ref>. The characteristic finding is blood leukocytosis with increase of dysplastic neutrophils and immature granulocytes. Bone marrow shows multilineage dysplasia.  

Atypical chronic myeloid leukemia, ''BCR-ABL1''-negative (aCML) presents with myelodysplastic as well as myeloproliferative features at the time of disease onset<ref name=":5" /><ref>Czader, M and Orazi, A. Chapter 45. Myelodysplastic/Myeloproliferative Neoplasms and Related Diseases. In Orazi A, Foucar K, Knowles DM. eds. Knowles Neoplastic Hematopathology. Riverwoods, IL: Wolters Kluwer Health; 2013:1148-1150.</ref>. The characteristic finding is blood leukocytosis with increase of dysplastic neutrophils and immature granulocytes. Bone marrow shows multilineage dysplasia.  

*Before the diagnosis of aCML can be rendered, myeloid neoplasms with well defined genetic abnormalities such as ''[[Chronic Myeloid Leukemia (CML), BCR-ABL1 Positive|BCR-ABL1]]'' fusion; rearrangement of [[Myeloid/Lymphoid Neoplasms with PDGFRA Rearrangement|P''DGFRA'']]'', [[Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement|PDGFRB]],'' ''[[Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement|FGFR1]]'', or ''[[Myeloid/Lymphoid Neoplasms with PCM1-JAK2|PCM1-JAK2]]'' must be ruled out.

*Before the diagnosis of aCML can be rendered, myeloid neoplasms with well defined genetic abnormalities such as ''[[HAEM5:Chronic myeloid leukaemia|BCR-ABL1]]'' fusion; rearrangement of [[HAEM5:Myeloid/lymphoid neoplasm with PDGFRA rearrangement|P''DGFRA'']]'', [[HAEM5:Myeloid/lymphoid neoplasm with PDGFRB rearrangement|PDGFRB]],'' ''[[HAEM5:Myeloid/lymphoid neoplasm with FGFR1 rearrangement|FGFR1]]'', or ''[[HAEM5:Myeloid/lymphoid neoplasm with JAK2 rearrangement|PCM1-JAK2]]'' must be ruled out.

*Myeloid neoplasm with features of aCML developed after chemo or radiation therapy is classified as [[Therapy-Related Myeloid Neoplasms|therapy-related myeloid neoplasm]].

*Myeloid neoplasm with features of aCML developed after chemo or radiation therapy is classified as [[HAEM5:Myeloid neoplasm post cytotoxic therapy|therapy-related myeloid neoplasm]].

==Synonyms / Terminology==

==Synonyms / Terminology==

==Epidemiology / Prevalence==

==Epidemiology / Prevalence==

The incidence of aCML is low; it is estimated that there are 1-2 aCML cases for every 100 cases of [[Chronic Myeloid Leukemia (CML), BCR-ABL1 Positive|''BCR-ABL1''-positive chronic myeloid leukemia]]<ref>{{Cite journal|last=A|first=Orazi|last2=U|first2=Germing|date=2008|title=The Myelodysplastic/Myeloproliferative Neoplasms: Myeloproliferative Diseases With Dysplastic Features|url=https://pubmed.ncbi.nlm.nih.gov/18480833/|language=en|pmid=18480833}}</ref><ref name=":0">{{Cite journal|last=Sa|first=Wang|last2=Rp|first2=Hasserjian|last3=Ps|first3=Fox|last4=Hj|first4=Rogers|last5=Jt|first5=Geyer|last6=D|first6=Chabot-Richards|last7=E|first7=Weinzierl|last8=J|first8=Hatem|last9=J|first9=Jaso|date=2014|title=Atypical Chronic Myeloid Leukemia Is Clinically Distinct From Unclassifiable Myelodysplastic/Myeloproliferative Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/24627528/|language=en|doi=10.1182/blood-2014-02-553800|pmc=PMC4067498|pmid=24627528}}</ref>.  

The incidence of aCML is low; it is estimated that there are 1-2 aCML cases for every 100 cases of [[HAEM5:Chronic myeloid leukaemia|''BCR-ABL1''-positive chronic myeloid leukemia]]<ref>{{Cite journal|last=A|first=Orazi|last2=U|first2=Germing|date=2008|title=The Myelodysplastic/Myeloproliferative Neoplasms: Myeloproliferative Diseases With Dysplastic Features|url=https://pubmed.ncbi.nlm.nih.gov/18480833/|language=en|pmid=18480833}}</ref><ref name=":0">{{Cite journal|last=Sa|first=Wang|last2=Rp|first2=Hasserjian|last3=Ps|first3=Fox|last4=Hj|first4=Rogers|last5=Jt|first5=Geyer|last6=D|first6=Chabot-Richards|last7=E|first7=Weinzierl|last8=J|first8=Hatem|last9=J|first9=Jaso|date=2014|title=Atypical Chronic Myeloid Leukemia Is Clinically Distinct From Unclassifiable Myelodysplastic/Myeloproliferative Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/24627528/|language=en|doi=10.1182/blood-2014-02-553800|pmc=PMC4067498|pmid=24627528}}</ref>.  

The median patient age at diagnosis is in the seventh or eighth decade of life<ref name=":0" /><ref name=":1">{{Cite journal|last=Jm|first=Hernández|last2=Mc|first2=del Cañizo|last3=A|first3=Cuneo|last4=Jl|first4=García|last5=Nc|first5=Gutiérrez|last6=M|first6=González|last7=G|first7=Castoldi|last8=Jf|first8=San Miguel|date=2000|title=Clinical, Hematological and Cytogenetic Characteristics of Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10847463/|language=en|pmid=10847463}}</ref><ref name=":2">{{Cite journal|last=P|first=Martiat|last2=Jl|first2=Michaux|last3=J|first3=Rodhain|date=1991|title=Philadelphia-negative (Ph-) Chronic Myeloid Leukemia (CML): Comparison With Ph+ CML and Chronic Myelomonocytic Leukemia. The Groupe Français De Cytogénétique Hématologique|url=https://pubmed.ncbi.nlm.nih.gov/2070054/|language=en|pmid=2070054}}</ref>. Rare cases of aCML has also been reported in teenagers. The reported male-to female ratio is approximately 1:1<ref name=":5">Orazi A, et al., (2017).  

The median patient age at diagnosis is in the seventh or eighth decade of life<ref name=":0" /><ref name=":1">{{Cite journal|last=Jm|first=Hernández|last2=Mc|first2=del Cañizo|last3=A|first3=Cuneo|last4=Jl|first4=García|last5=Nc|first5=Gutiérrez|last6=M|first6=González|last7=G|first7=Castoldi|last8=Jf|first8=San Miguel|date=2000|title=Clinical, Hematological and Cytogenetic Characteristics of Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/10847463/|language=en|pmid=10847463}}</ref><ref name=":2">{{Cite journal|last=P|first=Martiat|last2=Jl|first2=Michaux|last3=J|first3=Rodhain|date=1991|title=Philadelphia-negative (Ph-) Chronic Myeloid Leukemia (CML): Comparison With Ph+ CML and Chronic Myelomonocytic Leukemia. The Groupe Français De Cytogénétique Hématologique|url=https://pubmed.ncbi.nlm.nih.gov/2070054/|language=en|pmid=2070054}}</ref>. Rare cases of aCML has also been reported in teenagers. The reported male-to female ratio is approximately 1:1<ref name=":5">Orazi A, et al., (2017).  

*Trisomy 8 and del(20q) most common.

*Trisomy 8 and del(20q) most common.

*Abnormalities of chromosomes 13, 14, 17, 19 and 12 are also common <ref name=":1" /><ref name=":2" />.

*Abnormalities of chromosomes 13, 14, 17, 19 and 12 are also common <ref name=":1" /><ref name=":2" />.

*Isolated isochromosome 17q rare (most present with features of [[Chronic Myelomonocytic Leukemia (CMML)|CMML]] instead of aCML).

*Isolated isochromosome 17q rare (most present with features of [[HAEM5:Chronic myelomonocytic leukaemia|CMML]] instead of aCML).

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Mutations in ''TET2, ASXL1, EZH2'' and ''SRSF2'' (overlapping with [[Chronic Myelomonocytic Leukemia (CMML)|CMML]]) are not uncommon in aCML<ref>{{Cite journal|last=Faisal|first=Muhammad|last2=Stark|first2=Helge|last3=Büsche|first3=Guntram|last4=Schlue|first4=Jerome|last5=Teiken|first5=Kristin|last6=Kreipe|first6=Hans H.|last7=Lehmann|first7=Ulrich|last8=Bartels|first8=Stephan|date=2019|title=Comprehensive mutation profiling and mRNA expression analysis in atypical chronic myeloid leukemia in comparison with chronic myelomonocytic leukemia|url=http://doi.wiley.com/10.1002/cam4.1946|journal=Cancer Medicine|language=en|volume=8|issue=2|pages=742–750|doi=10.1002/cam4.1946|pmc=PMC6382710|pmid=30635983}}</ref>.

Mutations in ''TET2, ASXL1, EZH2'' and ''SRSF2'' (overlapping with [[HAEM5:Chronic myelomonocytic leukaemia|CMML]]) are not uncommon in aCML<ref>{{Cite journal|last=Faisal|first=Muhammad|last2=Stark|first2=Helge|last3=Büsche|first3=Guntram|last4=Schlue|first4=Jerome|last5=Teiken|first5=Kristin|last6=Kreipe|first6=Hans H.|last7=Lehmann|first7=Ulrich|last8=Bartels|first8=Stephan|date=2019|title=Comprehensive mutation profiling and mRNA expression analysis in atypical chronic myeloid leukemia in comparison with chronic myelomonocytic leukemia|url=http://doi.wiley.com/10.1002/cam4.1946|journal=Cancer Medicine|language=en|volume=8|issue=2|pages=742–750|doi=10.1002/cam4.1946|pmc=PMC6382710|pmid=30635983}}</ref>.

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