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| <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:Acute Undifferentiated Leukemia]]. | | <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:Acute Undifferentiated Leukemia]]. |
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| Amelia Nakanishi, MD and Shashi Shetty, PhD | | Amelia Nakanishi, MD and Shashi Shetty, PhD |
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| __TOC__
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| ==WHO Classification of Disease== | | ==WHO Classification of Disease== |
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| |} | | |} |
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| ==Definition / Description of Disease== | | ==Related Terminology== |
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| An acute leukemia with blasts that are immunophenotypically ambiguous for any one hematopoietic lineage. AUL is a diagnosis of exclusion that is incompatible with the presence of features that meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).
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| To support an undifferentiated phenotype, AUL requires an immunophenotypic work up that “excludes unusual lineages such as plasmacytoid dendritic cell precursors, natural killer precursors, basophils, and non-hematologic cells”<ref name=":0">Borowitz MJ, et al., (2017). Acute leukaemias of ambiguous lineage, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p182.</ref>.
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| ==Synonyms / Terminology==
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| Blast cell leukemia, stem cell leukemia, stem cell acute leukemia, undifferentiated leukemia.
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| ==Epidemiology / Prevalence==
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| Very rare; precise frequency unknown.
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| ==Clinical Features==
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| 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>
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| {| class="wikitable"
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| |'''Signs and Symptoms'''
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| |<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
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| <span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
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| <span class="blue-text">EXAMPLE:</span> Fatigue
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| <span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
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| |'''Laboratory Findings'''
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| |<span class="blue-text">EXAMPLE:</span> Cytopenias
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| <span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
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| <blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote>
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| In one study of 16 cases of adults with AUL, the median age was 63 years (range: 24-84 years) and patients could achieve clinical remission after allogeneic stem cell transplantation<ref name=":2">{{Cite journal|displayauthors=1|last=Heesch|first=Sandra|last2=Neumann|first2=Martin|last3=Schwartz|first3=Stefan|last4=Bartram|first4=Isabelle|last5=Schlee|first5=Cornelia|last6=Burmeister|first6=Thomas|last7=Hänel|first7=Matthias|last8=Ganser|first8=Arnold|last9=Heuser|first9=Michael|date=2013|title=Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization|url=https://pubmed.ncbi.nlm.nih.gov/23412561|journal=Annals of Hematology|volume=92|issue=6|pages=747–758|doi=10.1007/s00277-013-1694-4|issn=1432-0584|pmid=23412561|via=}}</ref>. In previous studies that weakly suggest ALL induction regimens over AML induction regimens, there may be selection bias in the patients who were well enough to be transplant candidates<ref>{{Cite journal|displayauthors=1|last=Weinberg|first=Olga K.|last2=Hasserjian|first2=Robert P.|last3=Baraban|first3=Ezra|last4=Ok|first4=Chi Young|last5=Geyer|first5=Julia T.|last6=Philip|first6=John K. S. S.|last7=Kurzer|first7=Jason H.|last8=Rogers|first8=Heesun J.|last9=Nardi|first9=Valentina|date=2019|title=Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group|url=https://pubmed.ncbi.nlm.nih.gov/31000771|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=32|issue=9|pages=1373–1385|doi=10.1038/s41379-019-0263-3|issn=1530-0285|pmid=31000771|via=}}</ref>.
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| In children, based on limited clinical information in the literature, AUL has been associated with a poor prognosis<ref>{{Cite journal|displayauthors=1|last=Lee|first=Hyun Gyung|last2=Baek|first2=Hee Jo|last3=Kim|first3=Ho Sung|last4=Park|first4=Soo Min|last5=Hwang|first5=Tai Ju|last6=Kook|first6=Hoon|date=2019|title=Biphenotypic acute leukemia or acute leukemia of ambiguous lineage in childhood: clinical characteristics and outcome|url=https://pubmed.ncbi.nlm.nih.gov/30956966|journal=Blood Research|volume=54|issue=1|pages=63–73|doi=10.5045/br.2019.54.1.63|issn=2287-979X|pmc=6439300|pmid=30956966|via=}}</ref>.
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| <blockquote class="blockedit">
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| <center><span style="color:Maroon">'''End of V4 Section'''</span>
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| ----
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| </blockquote>
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| ==Sites of Involvement==
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| Bone marrow and peripheral blood. AUL is so rare, it is unknown if there is a pattern of other sites of involvement.
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| ==Morphologic Features==
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| AUL blast morphology is bland and non-specific. Cytoplasmic granulation and disease defining morphology are absent.
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| ==Immunophenotype==
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| 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>
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| {| class="wikitable sortable"
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| !Finding!!Marker
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| |Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
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| |Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
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| |Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
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| |-
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| |Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
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| |}
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| <blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}</blockquote>
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| Per WHO 2017, AUL blasts should express no more than one membrane marker for any lineage.
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| {| class="wikitable sortable"
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| |Positive (universal)||Precursor stage''':''' HLA-DR, CD34, and/or CD38, CD117, CD133 <ref>Hoffman R, et al., (2018) Hematology, basic principles and practice, 7th edition. Elsevier: Philadelphia. (clinical key excerpt)</ref>
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| |Positive (subset)||TdT
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| CD7 (weak positivity) see below.
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| |Negative (universal)||Myeloid: MPO
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| Monocytic: NSE, CD11c, Cd14, CD64, lysozyme, Cd4, CD11b, CD36, NG2 homologue
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| T cell: cCD3
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| B cell: cCD22, cCD79a, strong CD19
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| Megakaryocytic: CD41, CD61, CD42, CD235a
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| |-
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| |Negative (subset)||NA
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| |}
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| Additional Description: Blasts are generally positive for HLA-DR, CD34, and/or CD38.
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| -CD7 positivity is associated with T cells, but can also be seen in some CD34+ hematopoietic stem cells and is not unexpected in a stem cell leukemia<ref name=":0" />.
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| -See [[HAEM4:Acute Leukemias of Ambiguous Lineage]] for assigning lineage assignment.
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| <blockquote class="blockedit">
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| <center><span style="color:Maroon">'''End of V4 Section'''</span>
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| ----
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| </blockquote>
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| ==WHO Essential and Desirable Genetic Diagnostic Criteria==
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| <span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
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| {| class="wikitable"
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| |WHO Essential Criteria (Genetics)*
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| |WHO Desirable Criteria (Genetics)*
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| |Other Classification
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| <nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
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| ==Related Terminology==
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| <span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
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| {| class="wikitable" | | {| class="wikitable" |
| |+ | | |+ |
| |Acceptable | | |Acceptable |
| | | | |N/A |
| |- | | |- |
| |Not Recommended | | |Not Recommended |
| | | | |Stem cell acute leukaemia |
| |} | | |} |
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| |} | | |} |
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| <blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote> |
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| NA | | NA |
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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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| * Gene Mutations (SNV/INDEL)}}</blockquote> | | * Gene Mutations (SNV/INDEL)}}</blockquote> |
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| There is evidence that the genes associated with poor prognosis in acute leukemias, BAALC, ERG, and MN1, are also overexpressed in AUL<ref name=":0" />. | | There is evidence that the genes associated with poor prognosis in acute leukemias, BAALC, ERG, and MN1, are also overexpressed in AUL<ref name=":0">Borowitz MJ, et al., (2017). Acute leukaemias of ambiguous lineage, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p182.</ref>. |
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| {| class="wikitable sortable" | | {| class="wikitable sortable" |
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| !Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)''' | | !Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s) |
| !'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T''' | | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T |
| !'''Established Clinical Significance Per Guidelines - Yes or No (Source)''' | | !Established Clinical Significance Per Guidelines - Yes or No (Source) |
| !'''Clinical Relevance Details/Other Notes''' | | !Clinical Relevance Details/Other Notes |
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| |<span class="blue-text">EXAMPLE:</span> | | |<span class="blue-text">EXAMPLE:</span> |
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| |} | | |} |
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| <blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote> |
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| NA | | NA |
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| !Chromosomal Pattern | | !Chromosomal Pattern |
| !Molecular Pathogenesis | | !Molecular Pathogenesis |
| !'''Prevalence -''' | | !Prevalence - |
| '''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
| | Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
| !'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T''' | | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T |
| !'''Established Clinical Significance Per Guidelines - Yes or No (Source)''' | | !Established Clinical Significance Per Guidelines - Yes or No (Source) |
| !'''Clinical Relevance Details/Other Notes''' | | !Clinical Relevance Details/Other Notes |
| |- | | |- |
| |<span class="blue-text">EXAMPLE:</span> | | |<span class="blue-text">EXAMPLE:</span> |
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| |} | | |} |
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| <blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote> |
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| AUL is associated with a high rate of chromosomal abnormalities, but have no characteristic abnormalities<ref name=":2" />. | | AUL is associated with a high rate of chromosomal abnormalities, but have no characteristic abnormalities<ref name=":2">{{Cite journal|displayauthors=1|last=Heesch|first=Sandra|last2=Neumann|first2=Martin|last3=Schwartz|first3=Stefan|last4=Bartram|first4=Isabelle|last5=Schlee|first5=Cornelia|last6=Burmeister|first6=Thomas|last7=Hänel|first7=Matthias|last8=Ganser|first8=Arnold|last9=Heuser|first9=Michael|date=2013|title=Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization|url=https://pubmed.ncbi.nlm.nih.gov/23412561|journal=Annals of Hematology|volume=92|issue=6|pages=747–758|doi=10.1007/s00277-013-1694-4|issn=1432-0584|pmid=23412561|via=}}</ref>. |
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| <blockquote class="blockedit"> | | <blockquote class="blockedit"> |
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| {| class="wikitable sortable" | | {| class="wikitable sortable" |
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| !Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -''' | | !Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence - |
| '''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
| | Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
| !'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T ''' | | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T |
| !'''Established Clinical Significance Per Guidelines - Yes or No (Source)''' | | !Established Clinical Significance Per Guidelines - Yes or No (Source) |
| !'''Clinical Relevance Details/Other Notes''' | | !Clinical Relevance Details/Other Notes |
| |- | | |- |
| |<span class="blue-text">EXAMPLE:</span>''EGFR'' | | |<span class="blue-text">EXAMPLE:</span>''EGFR'' |
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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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| <blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote> |
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| PHF6 a tumor suppressor gene may have implications in AUL though the evidence is limited. | | PHF6 a tumor suppressor gene may have implications in AUL though the evidence is limited. |
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| <blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote> |
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| Overexpression of BAALC, ERG, and MN1<ref name=":0" />. | | Overexpression of BAALC, ERG, and MN1<ref name=":0" />. |
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| (use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references /> | | (use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references /> |
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| ==Notes== | | ==Notes== |
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| <nowiki>*</nowiki>''Citation of this Page'': “Acute undifferentiated leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_undifferentiated_leukaemia</nowiki>. | | <nowiki>*</nowiki>''Citation of this Page'': “Acute undifferentiated leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_undifferentiated_leukaemia</nowiki>. |
| [[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]] | | [[Category:HAEM5]] |
| | [[Category:DISEASE]] |
| | [[Category:Diseases A]] |
