ANLL Flashcards
What is ANLL?
The blocked differentiation and unchecked proliferation of hematopoietic stem cells, resulting in the accumulation of blasts and replacement of normal hematopoietic precursors
ANLL is more common in children or adults?
Adults
T/F: patients who present with de novo AML have no identifiable risk factor
True
Some symptoms of ANLL include:
Hepatosplenomegaly
Enlarged lymph nodes
If WBC counts are very high => impairment of blood flow => neurological and pulmonary symptoms
If Central Nervous system is affected, patients can have headache
General lab findings of ANLL include? (3)
Normocytic normochromic anemia
Thrombocytopenia
Variable WBC counts
T/F: M0, M1, M2, M3 correspond to a granulocytic proliferation
True
T/F: M4 is related to granulocytic and erythroid lineages
False —> and monocytic
T/F: M5 is monocytic mainly, but could be mixed with other lineages
False —> Monocytic lineage only
M6 is of monocytic and erythroid mixed type
False —> granulocytic not monocytic
t/f: M7 is associated with acute megakaryoblastic leukemia
True
List the poor prognosis factors for ANLL:
Older age
CNS involvement
Systemic infection at diagnosis
WBC counts >100,000/mm3
Treatment induced AML
History of antecedent hematological disorder
Certain cytogenetic/molecular abnormalities (FLT3 gene mutation)
T/F: t (9; 22) is seen in some cases of ANLL (M0, M1,and less frequently M2 and M4) and is associated with a very bad prognosis
True
T/f: The myeloid nature of the blasts in M0 has to be demonstrated by immunological markers.
True, light microscopy and cytochemistry aren’t sufficient
What’s the mechanism that leads to maturation arrest in BM cells?
The mechanism involves activation of abnormal genes through chromosomal translocations and other genetic abnormalities
The cell developmental arrest leads to 2 complications that are?
1) Accumulation in liver, spleen, BM and blood due to increased proliferative rate and reduced apoptosis
2) Decrease in normal cell production leading to anemia, thrombocytopenia and neutrpenia
What are the most and least occurring ANLL subtypes?
M2 most (30%), M7 least (3%)
T/F: Trisomy 8 (8+) is a very frequent finding and associated with intermediate prognosis
True
What are the 4 genetic abnormalities associated with a poor prognosis in ANLL?
-7, 7q-, -5 and t (9; 22)
T/F: CD 17 is a myeloblast marker
False: CD117
How do you differentiate the myeloid nature of myeloblasts?
MPO, SBB and Auer rods positivity in type II (>3%) while negative in type I
How can you demonstrate the myeloid nature of blasts in M0? Why?
immunophenotyping: use of immunologic markers because they are minimally differentiated
What are the antigens expressed by M0 myeloblasts?
HLA-DR, TdT, CD13, CD33, CD34 and CD117
In which subtype(s) are 90% of NEC myeloblasts?
M0 and M1
Majority of blasts in M1 are type __?
1
T/F: In M2, less than 90% (but with a min. of 15%) of BM NEC are myeloblasts and the rest are maturing cells and monocytes. The monocytic precursors are <20% in BM and <5000/mm3 in PB
False —> minimum of 30%
Describe features of M2 blasts:
Mainly type II Often with Auer rods Large with relatively more N/C ratio than M0 and 1 Indented nucleus with large nucleoli Predominantly MPO and SBB +ve
Why is there no need for sbb and mpo staining for m2 blasts?
The blasts appear obviously mature with primary granules
What do you expect to find in M2 BM smear?
Promyelocytes, myelocytes and mature neutrophils with variable dysplasia and nuclear abnormalities (ex: PPH nucleus)
M2 blast are positive for the following Ags:
HLA-DR, CD13, CD33, CD34, CD117 and MPO
T/F: M2 has better prognosis than M1
True
What do you expect to find in BM in M2 eos variant? What is its prognosis like?
Excess of abnormal large eosinophils with dark bluish granules and some reddish ones. Excellent prognosis.
The ETO (t (8; 21)) translocation is found in M2 only? What happens? Which surface Ag is frequently co-expressed with it?
No, also found in M1 and M4.
The ETO gene on ch. 8 and the AML1 gene on ch. 21 undergo translocation leading to the formation of the hybrid gene AML1-ETO which confers the patient with longer survival. The CD-19 B-cell specific Ag is often co-expressed in t(8; 21)
In addition to t(8; 21) what chromosomal might you encounter in M2?
Trisomy 8, monosomy 7, 7q-, monosomy 5 and 5q-
APL is associated with the __ subtype and caused by ___ of leukocyte differentiation at the ___ stage. Also, ___ % of BM NEC are ___.
M3, arrest, promyelocyte, >50% , promyelocytes
What are the 2 variants of M3 APL? Describe them
Hyper-granular: bilobed nuclei, course granules that may overlie the nucleus and low to norm WBC
Hypo-granular: folded/kidney shaped nucleus, occurs mainly in children and has poor prognosis, high WBC count (up to 200,000/mm3)
What is the clinical significance of M3? How do you prevent the complications it causes? Do M3 patients respond well to treatment?
Associated with blood clotting (DIC) due to procoagulants in the cytoplasmic granules especially during treatment as the cells are lysed releasing their granules.
Can be prevented by heparinizing the patient before treatment, which will allow for a good response.
What chromosomal anomaly is found in >95% of cases of APL? What hybrid gene does it result in? Why is it important to identify? How can it be treated? Is this treatment enough alone to ensure no remission and why?
T(15; 27) (q22; q21), results in PML-RAR gene.
This translocation results in blockage of retinoic acid production which is needed for myeloid differentiation. This can be treated with ATRA which induces promyelocyte differentiation and hence greatly reduces the leukemic cells enough to reach remission. However, ATRA should be followed by chemo to ensure no relaspse occurs as it doesn’t eliminate the leukemic clone.
Do patients without t(15; 27) but with t(11; 17) respond to ATRA?
No
Can ALP patients with t(5; 17) respond to ATRA?
Yes
T/F: M3 myeloblasts are HLA-DR and CD34 negative
True
What Ags do M3 blasts express?
CD13, 33 and 117
T/F: Both M4 and M5 are associated with infiltration of mucous membrane and CNS involvement
True
T/F: M4 is a mixed type of myeloid and monocytic leukemia that has stem cell involvement
True
Why BM NEC monocytic cells shouldn’t exceed 80% in M4?
It’ll be considered as the M5 subtype
What Ags do M4 cells express?
HLA-DR, MPO, CD 13, 14, 33 and 117
What will you see in PB of an M4 patient?
A very high # of WBCs of which 5000/mm3 are monocytes at least
Predominantly monocytic population with monoblasts, promonocytes and monocytes
T/F: M4 chromosomal translocations are associated with #16
True
T/F: There is an M4 variant with eosinophilia that’s characterized by abnormal eosinophils with dysplastic granules that are large, irregular and dark staining
True
What are the M4 chromosomal anomalies?
Inv (16) (p13; q22), t(16; 16) (p13; q22), del(16) (q22) and 16q-
Why is m4 eos imp to identify?
Has better prognosis than normal m4
In case of M5 more than __ of BM NEC are ___. There are 2 types, M5a that involves___ and M5b that involves___
> 80%, monocytic cells, immature monoblasts, monocytes
Moncyte-specific Ags are?
CD11b and CD14, in addition to CD13, 33 and 64 that are shared by all monocytic stages
What nuclear abnormalities can be seen in M6 (AEL)?
Multiple lobulation in nucleus of erythroblasts with difference in lobe size and multiple nuclei
M6 RBCs are PAS ___ and stain in ___ in immature stages and ____ in mature stages
Positive, blocks, diffusely
Erythroblast Ags include:
CD71, glycophorin A and variability in HLA-DR
M6 myeloblasts express what Ags?
HLA-DR, MPO, CD13, CD33 and CD117, variable for CD34
T/F: M7 is characterized by rapidly progressive proliferation of atypical megakaryocytes and their precursor cells
True
T/F: In PB of an M7 patient, the number of circulating blasts is small
True
Why can’t you get a BM aspirate from an M7 patient? What do you do instead?
Myelofibrosis due to PDGF that stimulates fibrous tissue formation in BM
Take a bone biopsy
What is the enzyme used to identify M7? Where in the cell will you see it stained?
Platelet peroxidase which is only found in megakaryocytic cells. It stains in the nuclear envelope and ER
What Ags are expressed by megakaryocytic cells of M7?
Glycoprotein 2b and 3a, CD41 and CD61
Define MDS
- group of diseases in which the production of blood cells by the BM is disrupted
- the BM is typically more active than normal and yet the numbers of blood cells in the circulation are reduced
List the 5 types of MDS according to FAB classification
1) Blasts < 5% = RA
2) Blasts <5% and sideroblastic rings >15% = RARS
3) Blasts >5% but less than <20% = RAEB
4) Blasts >20% but less than 30% = RAEB-T
5) Blasts >5% but less than 20% with increase in monocytes (>1000/mm3) = CMML
