Myeloproliferative Disorders - Revision history

Admin at 21:42, 6 March 2024

2024-03-06T21:42:56Z

← Older revision		Revision as of 17:42, 6 March 2024
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	* ↑ tyrosine kinase activity		* ↑ tyrosine kinase activity
	\|		\|
			* Significant neutrophilia and left shift
	\|		\|
	* Significant neutrophilia and left shift
	* Myeloid hyperplasia, M:E ratio 10:1		* Myeloid hyperplasia, M:E ratio 10:1
	\|		\|
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	\|JAK2, CALR, or MPL mutation		\|JAK2, CALR, or MPL mutation
	\|		\|
			* Thrombocytosis
			* Abnormal platelet aggregation
			* Abnormal platelet forms (giant platelets, megakaryocyte fragments)
			* Neutrophilia, slight left shift
	\|		\|
			* Megakaryocytic hypercellularity
	\|Must not match any other MPD criteria or be caused by reactive thrombocytosis		\|Must not match any other MPD criteria or be caused by reactive thrombocytosis

Admin at 21:36, 6 March 2024

2024-03-06T21:36:59Z

← Older revision		Revision as of 17:36, 6 March 2024
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	{\| class="wikitable"		{\| class="wikitable"
	\|+		\|+
	!Condition		! rowspan="2" \|Condition
	!Cause		! rowspan="2" \|Cause
	!Lab Findings		! colspan="2" \|Lab Findings
	!Diagnostic Tests		! rowspan="2" \|Diagnostic Tests
	!Treatment		! rowspan="2" \|Treatment
			\|-
			!Peripheral Blood
			!Bone Marrow
	\|-		\|-
	\|Chronic Myelogenous Leukemia		\|Chronic Myelogenous Leukemia
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	* BCR/ABL fusion		* BCR/ABL fusion
	* ↑ tyrosine kinase activity		* ↑ tyrosine kinase activity
			\|
	\|		\|
	* Significant neutrophilia and left shift		* Significant neutrophilia and left shift
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	\|		\|
	* Absolute erythrocytosis		* Absolute erythrocytosis
	* ~~Decreased EPO~~		* Moderate leukocytosis
	* Moderate ~~leukocytosis and~~ thrombocytosis		* Moderate thrombocytosis
			* ↓ EPO (serum)
			\|
	* BM myelopoiesis		* BM myelopoiesis
	\|		\|
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	\|Essential Thrombocythemia		\|Essential Thrombocythemia
	\|JAK2, CALR, or MPL mutation		\|JAK2, CALR, or MPL mutation
			\|
	\|		\|
	\|Must not match any other MPD criteria or be caused by reactive thrombocytosis		\|Must not match any other MPD criteria or be caused by reactive thrombocytosis
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	\|-		\|-
	\|Primary Myelofibrosis		\|Primary Myelofibrosis
			\|JAK2 (60%)

			* Abnormal megakaryocyte growth stimulates collagen
			* Fibrotic material invade BM and eventually other tissues
	\|		\|
			* Immature granulocytes
			* NRBCs
			* Teardrops/abnormal poik
			* Giant platelets
			* Micromegakaryocytes
	\|		\|
			* Initially, hypercellular marrow with abnormal megakaryocytes
			* Reticulin fibrosis
			* Progressive marrow failure with fibrosis
			\|Must not match any other MPD criteria

			* BM biopsy: Megakaryocyte proliferation with reticulin and/or collagen fibrosis
			* JAK2, CALR, or MPL mutation (or another marker)
			* BM aspirate "dry tap"
	\|		\|
	\|		* Stem cell transplants
			* Chemotherapy
			* JAK2 inhibitors
	\|}		\|}
	~~General Features~~

			==== General Features ====
	* Tend to affect adult and geriatric populations		* Tend to affect adult and geriatric populations
	* Begin as chronic disorders, which may transform into subacute, and then acute disorders		* Begin as chronic disorders, which may transform into subacute, and then acute disorders
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	*** ↑ serum B12 (due to ↑ breakdown of WBCs)		*** ↑ serum B12 (due to ↑ breakdown of WBCs)

	Polycythemia Vera		==== Polycythemia Vera ====

	* Caused by substitution in JAK2 gene (90-97% caused by V617F)		* Caused by substitution in JAK2 gene (90-97% caused by V617F)
	** Mutated protein is active without requiring erythropoietin		** Mutated protein is active without requiring erythropoietin
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	**** Moderate leukocytosis and thrombocytosis		**** Moderate leukocytosis and thrombocytosis

	Essential Thrombocythemia		==== Essential Thrombocythemia ====

	* Marked thrombocytosis >450x10^9L		* Marked thrombocytosis >450x10^9L
	* Large masses of platelet aggregates		* Large masses of platelet aggregates
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	** BM: Megakaryopoiesis (large, mature megakaryocytes with no other increases in cell types)		** BM: Megakaryopoiesis (large, mature megakaryocytes with no other increases in cell types)
	** Genetics		** Genetics
	*** ~~JAC2~~, CALR, or MPL mutations		*** JAK2, CALR, or MPL mutations

			==== Primary Myelofibrosis ====

			* Abnormal megakaryocyte growth stimulates collagen production by BM fibroblasts
			** JAK2 V617F associated with 60% of cases
			** Fibrinoblastic growth factors support collagen production
			** BM tissue is replaced with fibrous materials, causing fibrosis
			** BM failure develops are cellularity is lost
			* Extramedullary hematopoiesis
			** Infiltration of BM with fibrous materials results in stem cells being push out into other tissue
			** Hematopoiesis begins occurring outside of BM
			*** Accumulation of cells in spleen, liver, and other organs
			** Can cause fibrosis of other organs (e.g., spleen)
			*** anemia, thrombocytopenia
			* Lab Results:
			** Bone Marrow
			*** "Dry tap" where no aspirate is collected
			*** BM biopsy showing fibrosis in >1/3 of biopsy section
			* Myelofibrosis
			** Increased fine fibres (reticulin, type III collagen)
			* Myelosclerosis
			** increased coarse, type I collagen
			* Treatment
			** Stem cell transplants
			** Splenectomy
			** Chemotherapy
			** JAK2 inhibitors

Admin: Created page with "Myeloproliferative disorders are stem cell disorders that that result in excess production and overaccumulation of erythrocytes, granulocytes, and/or platelets. These abnormalities may appear in bone marrow, peripheral blood, and body tissues. The main types include: # Chronic myelogenous leukemia (CML) # Polycythemia vera (PV) # Essential thrombocythemia (ET) # Primary myelofibrosis (PMF) {| class="wikitable" |+ !Condition !Cause !Lab Findings !Diagnostic Tests !Trea..."

2024-03-06T20:42:55Z

Created page with "Myeloproliferative disorders are stem cell disorders that that result in excess production and overaccumulation of erythrocytes, granulocytes, and/or platelets. These abnormalities may appear in bone marrow, peripheral blood, and body tissues. The main types include: # Chronic myelogenous leukemia (CML) # Polycythemia vera (PV) # Essential thrombocythemia (ET) # Primary myelofibrosis (PMF) {| class="wikitable" |+ !Condition !Cause !Lab Findings !Diagnostic Tests !Trea..."

New page

Myeloproliferative disorders are stem cell disorders that that result in excess production and overaccumulation of erythrocytes, granulocytes, and/or platelets. These abnormalities may appear in bone marrow, peripheral blood, and body tissues.

The main types include:

# Chronic myelogenous leukemia (CML)
# Polycythemia vera (PV)
# Essential thrombocythemia (ET)
# Primary myelofibrosis (PMF)

{| class="wikitable"
|+
!Condition
!Cause
!Lab Findings
!Diagnostic Tests
!Treatment
|-
|Chronic Myelogenous Leukemia
|t(9,22)

* BCR/ABL fusion
* ↑ tyrosine kinase activity
|
* Significant neutrophilia and left shift
* Myeloid hyperplasia, M:E ratio 10:1
|
* PBF/BM
* Cytogenetics or molecular genetics for t(9,22)
** PCR for BCR/ABL
* LAP testing (lack activity, score <13)
|
* BM/stem cell transplants
* Chemotherapy
* Tyrosine kinase inhibitors
|-
|Polycythemia Vera
|JAK2 mutation (V617F)

* grow in absence of erythropoietin
* divide normally, but do not undergo apoptosis
|
* Absolute erythrocytosis
* Decreased EPO
* Moderate leukocytosis and thrombocytosis
* BM myelopoiesis
|
* JAK2 mutation
* ↑ HGB
* BM Hypercellularity
* Decreased serum EPO
|
* Therapeutic phlebotomy
* Hydroxyuria treatment (myelosuppressive drugs)
* JAK2 inhibitors
|-
|Essential Thrombocythemia
|JAK2, CALR, or MPL mutation
|
|Must not match any other MPD criteria or be caused by reactive thrombocytosis

* ↑ platelets >450x10^9/L
* BM: megakaryopoiesis
* JAK2, CALR, or MPL mutation
|
* Suppress BM megakaryocyte production
* Hydroxuria treatment (suppresses platelets in PB)
|-
|Primary Myelofibrosis
|
|
|
|
|}
General Features

* Tend to affect adult and geriatric populations
* Begin as chronic disorders, which may transform into subacute, and then acute disorders
** Subacute
** Acute: aggressive growth (acute myeloid leukemia)
* May cause marrow hypoplasia/depletion of cells
* Common lab features:
** Splenomegaly (60-100%)
** Cytogenetic abnormalities

==== Chronic Myelogenous Leukemia ====

* caused by translocation of genes in pluripotent hematopoietic stem cells
** Philadelphia chromosome (Ph) in >90% of leukemic cells
** reciprocal translocation between chromosomes 9 and 22. t(9,22)
** BCR/ABL fusion proteins affect tyrosine kinase activity
*** Unregulated cell growth, failure to undergo apoptosis
* clonal overproduction of myeloid cell line
** increased immature neutrophils
* Has 3 phases:
** Chronic: <10% blasts
** Accelerated: 10-19% blasts, basophilia in peripheral blood
** Acute: >20% blasts
* Lab findings:
** Peripheral Blood:
*** Neutrophilia, with all phases of maturation
**** Leukocytosis
**** Left shift (promyelocytes and blasts)
*** Basophilia
*** Eosinophilia
*** Thrombocytosis
** Bone Marrow:
*** Myeloid hyperplasia
*** Hypercellularity
*** M:E ratio increased (10:1)
** Chemistry
*** ↑ uric acid (due to ↑ cell turnover)
*** ↑ lactate dehydrogenase
*** ↑ serum B12 (due to ↑ breakdown of WBCs)

Polycythemia Vera

* Caused by substitution in JAK2 gene (90-97% caused by V617F)
** Mutated protein is active without requiring erythropoietin
** Upregulation of anti-apoptotic protein
** Cell divides normally but doesn't undergo apoptosis
* Signs and Symptoms:
** Ruddy cyanosis (reddish-purple colour to face)
** Vascular complications
** Splenomegaly
** Lab Findings:
*** Peripheral Blood:
**** Absolute erythrocytosis
**** ↑ HGB, HCT
**** IDA may develop
**** Moderate leukocytosis and thrombocytosis

Essential Thrombocythemia

* Marked thrombocytosis >450x10^9L
* Large masses of platelet aggregates
* Abnormal platelet morphology
** Giant platelets, megakaryocyte fragments
* Possibly ↑ WBC (neutrophilia with slight left shift)
* Lab Findings:
** Abnormal coagulation studies
*** Abnormal platelet aggregation
** BM: Megakaryopoiesis (large, mature megakaryocytes with no other increases in cell types)
** Genetics
*** JAC2, CALR, or MPL mutations