Paediarics Flashcards
(33 cards)
What does JMML stand for?
Juvenile Myelomonocytic Leukemia
JMML is a type of myeloproliferative neoplasm primarily affecting children.
What is the primary age group affected by JMML?
Children aged 0-14, predominantly ages 2-4
JMML mainly occurs in young children.
What is the gender predominance in JMML cases?
Male predominance
More males are diagnosed with JMML compared to females.
What kind of genetic lesion is associated with JMML?
RAS activating genetic lesion in haematopoietic stem cells
This lesion leads to constitutively activated RAS signaling.
What is the effect of RAS activation on myeloid progenitors?
Increases sensitivity to granulocyte-monocyte-colony-stimulating-factor
This sensitivity contributes to the characteristics of JMML.
What are some inherited syndromes associated with JMML?
NF1, CBL, Noonan syndrome
These syndromes may require a somatic second hit in the haematopoietic compartment.
List some clinical features of JMML.
- Pallor and fever
- Hepatosplenomegaly
- Lymphadenopathy
- Rash
- Myeloid sarcoma of CNS
These symptoms can vary in severity among patients.
What are the clinical features of NF1 associated with JMML?
- Café au lait spots
- Xanthomas
NF1 is a genetic condition that can present with skin manifestations.
What are the clinical features of Noonan syndrome associated with JMML?
- Facial dysmorphia
- Cardiac defects
- Lymphatic effusions
Noonan syndrome presents various physical and health issues.
What findings would you expect in a complete blood examination (CBE) for JMML?
Leukocytosis >10, including monocytosis >1.0
Typically, neutrophilia may also be present.
What is the typical blast percentage in peripheral blood for JMML?
Usually up to 2% blasts
Blasts are immature blood cells and their presence is monitored.
What are the bone marrow biopsy findings in JMML?
- Myeloid hyperplasia with maturation
- Minimal/no dysplasia
- <20% blasts
- Reduced megakaryocytes
- Marked monocytic infiltrate
These morphological features help confirm a diagnosis.
What aberrant expression is noted in flow cytometry for JMML?
Aberrant blasts expressing CD7 with reduced CD13 and 33
These markers help in the identification of JMML.
What karyotype abnormalities might be found in JMML?
Normal or monosomy 7 in 25% of cases
Monosomy 7 is more common with KRAS mutations.
What is recommended if common driver mutations are negative?
FISH to look for fusions causing upstream activation of RAS
FISH is a genetic testing method used to detect specific DNA sequences.
What is the diagnostic criterion regarding peripheral monocytosis for JMML?
Peripheral monocytosis >1.0 x10^9
This criterion is essential for diagnosis.
What is the maximum blast percentage allowed in peripheral blood and bone marrow for a JMML diagnosis?
Blasts <20%
This threshold helps in differentiating JMML from other leukemias.
What are the genetic criteria for diagnosing JMML?
RAS pathway activating mutation: KRAS, NRAS, PTPN11, NF1, CBL
These mutations are critical for the pathophysiology of JMML.
Fill in the blank: RAS pathway activating mutations may be somatically acquired in _____ or inherited in the context of a RASopathy _____ %.
60%, 20-30%
This highlights the genetic aspect of the disease.
List additional criteria for JMML if unable to meet primary diagnostic criteria.
- Increased HbF for age
- LEBP
- Typical bone marrow morphology
- Hypersensitivity of myeloid progenitors to GM-CSF demonstrated in vitro
These criteria assist in cases where the primary criteria are not fully met.
What is Diamond Blackfan Anaemia (DBA)?
An inherited bone marrow failure that results in predominantly red cell aplasia and is caused by ribosomal protein gene mutations, most commonly RPS19.
What is the inheritance pattern of DBA?
45% autosomal dominant, others sporadic.
What is the pathophysiology of DBA?
Defective ribosome biogenesis > impaired proliferation and differentiation of erythroid precursors, upregulation of p53 pathway leading to apoptosis.
When does DBA typically present?
In the 1st year of life.
