Acute promyelocytic leukemia pathophysiology: Difference between revisions

Jump to navigation Jump to search
← Older editNewer edit →
VisualWikitext
Shyam Patel (talk | contribs)
nocaptcha
3,105 edits
Shyam Patel (talk | contribs)
nocaptcha
3,105 edits
No edit summary
Line 13: Line 13:
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Chromosomal Location}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Chromosomal Location}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Function}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Function}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Response to Therapy}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Other Features}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Other Features}}
|-
|-
Line 24: Line 25:
*Regulate p53 response to oncogenic growth signals
*Regulate p53 response to oncogenic growth signals
*Influenced by the cell cycle
*Influenced by the cell cycle
| style="padding: 5px 5px; background: #F5F5F5;" |
*Sensitive to all-''trans'' retinoic acid<ref name="pmid23556100">{{cite journal| author=Park J, Jurcic JG, Rosenblat T, Tallman MS| title=Emerging new approaches for the treatment of acute promyelocytic leukemia. | journal=Ther Adv Hematol | year= 2011 | volume= 2 | issue= 5 | pages= 335-52 | pmid=23556100 | doi=10.1177/2040620711410773 | pmc=3573416 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23556100  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Most common translocation
*Most common translocation
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
''PLZF'' (''ZBTB16'')
''PLZF'' (''ZBTB16'')<ref name="pmid28529810">{{cite journal| author=Langabeer SE, Preston L, Kelly J, Goodyer M, Elhassadi E, Hayat A| title=Molecular Profiling: A Case of ZBTB16-RARA Acute Promyelocytic Leukemia. | journal=Case Rep Hematol | year= 2017 | volume= 2017 | issue=  | pages= 7657393 | pmid=28529810 | doi=10.1155/2017/7657393 | pmc=5424191 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28529810  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
11q23.2
11q23.2
Line 35: Line 38:
*Involved in cell cycle regulation
*Involved in cell cycle regulation
*Interacts with histone deacetylases
*Interacts with histone deacetylases
| style="padding: 5px 5px; background: #F5F5F5;" |
*Resistant to all-''trans'' retinoic acid<ref name="pmid23556100">{{cite journal| author=Park J, Jurcic JG, Rosenblat T, Tallman MS| title=Emerging new approaches for the treatment of acute promyelocytic leukemia. | journal=Ther Adv Hematol | year= 2011 | volume= 2 | issue= 5 | pages= 335-52 | pmid=23556100 | doi=10.1177/2040620711410773 | pmc=3573416 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23556100  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Second most common translocation (after ''PML-RARA'')
*Second most common translocation (after ''PML-RARA'')
Line 48: Line 53:
*Regulates the cell cycle
*Regulates the cell cycle
*Sequesters the tumor suppressor ''ARF'' in the nucleus and protects ''ARF'' from degradation
*Sequesters the tumor suppressor ''ARF'' in the nucleus and protects ''ARF'' from degradation
| style="padding: 5px 5px; background: #F5F5F5;" |
*Sensitive to all-''trans'' retinoic acid<ref name="pmid23556100">{{cite journal| author=Park J, Jurcic JG, Rosenblat T, Tallman MS| title=Emerging new approaches for the treatment of acute promyelocytic leukemia. | journal=Ther Adv Hematol | year= 2011 | volume= 2 | issue= 5 | pages= 335-52 | pmid=23556100 | doi=10.1177/2040620711410773 | pmc=3573416 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23556100  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*''NPM1'' mutation carries a favorable prognosis in [[acute myeloid leukemia]]
*''NPM1'' mutation carries a favorable prognosis in [[acute myeloid leukemia]]
Line 53: Line 60:
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
''NUMA''
''NUMA''<ref name="pmid23556100">{{cite journal| author=Park J, Jurcic JG, Rosenblat T, Tallman MS| title=Emerging new approaches for the treatment of acute promyelocytic leukemia. | journal=Ther Adv Hematol | year= 2011 | volume= 2 | issue= 5 | pages= 335-52 | pmid=23556100 | doi=10.1177/2040620711410773 | pmc=3573416 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23556100  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
11q13.4
11q13.4
Line 60: Line 67:
*Interacts with microtubules
*Interacts with microtubules
*Contributes to mitotic spindle formation during cell division
*Contributes to mitotic spindle formation during cell division
| style="padding: 5px 5px; background: #F5F5F5;" |
*Sensitive to all-''trans'' retinoic acid<ref name="pmid23556100">{{cite journal| author=Park J, Jurcic JG, Rosenblat T, Tallman MS| title=Emerging new approaches for the treatment of acute promyelocytic leukemia. | journal=Ther Adv Hematol | year= 2011 | volume= 2 | issue= 5 | pages= 335-52 | pmid=23556100 | doi=10.1177/2040620711410773 | pmc=3573416 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23556100  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Rare translocation
*Rare translocation
Line 74: Line 83:
*Involved in [[apoptosis]]
*Involved in [[apoptosis]]
*Sequesters the tumor suppressor ''ARF'' in the nucleus and protects ''ARF'' from degradation
*Sequesters the tumor suppressor ''ARF'' in the nucleus and protects ''ARF'' from degradation
| style="padding: 5px 5px; background: #F5F5F5;" |
*Resistant to all-''trans'' retinoic acid<ref name="pmid23556100">{{cite journal| author=Park J, Jurcic JG, Rosenblat T, Tallman MS| title=Emerging new approaches for the treatment of acute promyelocytic leukemia. | journal=Ther Adv Hematol | year= 2011 | volume= 2 | issue= 5 | pages= 335-52 | pmid=23556100 | doi=10.1177/2040620711410773 | pmc=3573416 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23556100  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Rare translocation
*Rare translocation

Revision as of 22:18, 10 May 2018

Acute promyelocytic leukemia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Acute promyelocytic leukemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Other Imaging Studies

Other Diagnostic Studies

Treatment

Medical Therapy

Interventions

Surgery

Primary PreventionSurgery

Secondary PreventionSurgery

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Acute promyelocytic leukemia pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Acute promyelocytic leukemia pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Acute promyelocytic leukemia pathophysiology

CDC on Acute promyelocytic leukemia pathophysiology

Acute promyelocytic leukemia pathophysiology in the news

Blogs on Acute promyelocytic leukemia pathophysiology

Directions to Hospitals Treating Acute promyelocytic leukemia

Risk calculators and risk factors for Acute promyelocytic leukemia pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Pathophysiology

The pathophysiology of acute promyelocytic leukemia begins with a balanced reciprocal chromosomal translocation in hematopoietic stem cells. The chromosomal translocation involves the juxtaposition of the retinoic acid receptor-alpha gene (RARA) on the long arm of chromosome 17 with another gene, most commonly the promyelocytic leukemia gene (PML) on the long arm of chromosome 15.[1] The translocation is designated as t(15;17)(q22;q12). The PML-RARA fusion product is a transcriptional regulator and prevents myeloid differentiation. This is known as a differentiation block, since the cells are unable to differentiate into normal mature cells. The result of the chromosomal translocation is ineffective blood cell production and uncontrolled proliferation of malignant promyelocytes.[1] In 95% of cases of acute promyelocytic leukemia, the translocation involved PML and RARA. However, it is important to note that RARA has multiple other binding partners which can lead to the development or acute promyelocytic leukemia, as shown in the table below.


Translocation Partner Chromosomal Location Function Response to Therapy Other Features

PML

15q24.1

  • A member of the tripartite motif (TRIM) family
  • Localizes to nucleolar bodies and functions as a transcription factor and tumor suppressor
  • Regulate p53 response to oncogenic growth signals
  • Influenced by the cell cycle
  • Sensitive to all-trans retinoic acid[2]
  • Most common translocation

PLZF (ZBTB16)[1]

11q23.2

  • Encodes a zinc finger transcription factor
  • Involved in cell cycle regulation
  • Interacts with histone deacetylases
  • Resistant to all-trans retinoic acid[2]
  • Second most common translocation (after PML-RARA)

NPM1

5q35.1

  • Encodes nucleophosmin 1 (a nucleolar shuttle protein)
  • Involved in centromere duplication
  • Serves a protein chaperone
  • Regulates the cell cycle
  • Sequesters the tumor suppressor ARF in the nucleus and protects ARF from degradation
  • Sensitive to all-trans retinoic acid[2]

NUMA[2]

11q13.4

  • Contributes to a structural component of the nuclear matrix
  • Interacts with microtubules
  • Contributes to mitotic spindle formation during cell division
  • Sensitive to all-trans retinoic acid[2]
  • Rare translocation

STAT5B

17q21.2

  • Encodes a signal transducer and activator of transcription (STAT)
  • Serves an intracellular transduction molecule for cytokine signaling
  • Translocates to the nucleus and functions as a transcription factor
  • Involved in T cell receptor signaling
  • Involved in apoptosis
  • Sequesters the tumor suppressor ARF in the nucleus and protects ARF from degradation
  • Resistant to all-trans retinoic acid[2]
  • Rare translocation

References

  1. ↑ 1.0 1.1 1.2 Langabeer SE, Preston L, Kelly J, Goodyer M, Elhassadi E, Hayat A (2017). "Molecular Profiling: A Case of ZBTB16-RARA Acute Promyelocytic Leukemia". Case Rep Hematol. 2017: 7657393. doi:10.1155/2017/7657393. PMC 5424191. PMID 28529810.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Park J, Jurcic JG, Rosenblat T, Tallman MS (2011). "Emerging new approaches for the treatment of acute promyelocytic leukemia". Ther Adv Hematol. 2 (5): 335–52. doi:10.1177/2040620711410773. PMC 3573416. PMID 23556100.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Acute_promyelocytic_leukemia_pathophysiology&oldid=1470036"