Tag: Acute myeloid leukemia (AML)

Acute myeloid leukemia (AML)

Acute myeloid leukemia (AML)

Q. 1

Non-specific esterase is positive in all the categories of Acute Myeloid Leukemia, EXCEPT:

 A

M3

 B

M4

 C

M5

 D

M6

Q. 1

Non-specific esterase is positive in all the categories of Acute Myeloid Leukemia, EXCEPT:

 A

M3

 B

M4

 C

M5

 D

M6

Ans. A

Explanation:

Non specific esterase is negative in M3 type of Acute myeloid leukemia (AML).

Alpha naphthyl acetate esterase (ANAE), Alpha naphthyl butyrate esterase (ANBE) and Alpha naphthyl AS esterase (NASA) are the non specific esterase reactions that are positive in M4 (acute myelomonocytic leukemia) and M5 (acute monocytic/monoblastic leukemia) type of AML.

Their presence is variable in M6 (acute erythroid leukemia).

Ref: Wintrobe’s Clinical Hematology, 10th Ed, Page 2221; Textbook of pathology, B N Datta, 2nd Edition, Page 1118 & 1119.


Q. 2

A 32 year old male is diagnosed of having acute myeloid leukemia. His total WBC count was less than normal initially. Which of the following factor has a bad prognosis in AML?

 A

Monosomies of chromosomes

 B

Young age

 C

Patients with t(15;17)

 D

Low WBC count

Q. 2

A 32 year old male is diagnosed of having acute myeloid leukemia. His total WBC count was less than normal initially. Which of the following factor has a bad prognosis in AML?

 A

Monosomies of chromosomes

 B

Young age

 C

Patients with t(15;17)

 D

Low WBC count

Ans. A

Explanation:

Prognostic factors of acute myeloid leukemia (AML):

  • Advancing age is associated with a poorer prognosis, in part because of its influence on the patient’s ability to survive induction therapy.
  • The leukemic cells in elderly patients more commonly express the multidrug resistance 1 (MDR1) efflux pump that conveys resistance to natural product–derived agents such as the anthracyclines.
  • Patients with t(15;17) have a very good prognosis, and those with t(8;21) and inv(16) a good prognosis, while those with no cytogenetic abnormality have a moderately favorable outcome.
  • Patients with a complex karyotype, t(6;9), inv(3), or -7 have a very poor prognosis.
  • Among patients with hyperleukocytosis (>100,000/L), early central nervous system bleeding and pulmonary leukostasis contribute to poor outcome with initial therapy.
  • Karyotypes include monosomy chromosome 5 or chromosome 7 have 78% of relapse rate.
 
Ref: Wetzler M., Marcucci G., Bloomfield C.D. (2012). Chapter 109. Acute and Chronic Myeloid Leukemia. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

Q. 3

All of the following genetic syndromes are associated with Acute Myeloid Leukemia, except:

 A

Down’s Syndrome

 B

Klinefelter’s Syndrome

 C

Patau Syndrome

 D

Turner’s Syndrome

Q. 3

All of the following genetic syndromes are associated with Acute Myeloid Leukemia, except:

 A

Down’s Syndrome

 B

Klinefelter’s Syndrome

 C

Patau Syndrome

 D

Turner’s Syndrome

Ans. D

Explanation:

Of all the options given Turner’s syndrome is not found to be associated with increased incidence of acute myeloid leukemia (AML). Down’s syndrome, Klinefelter’s Syndrome, Patau Syndrome are associated with AML.

Ref: Harrison’s Principles of Internal Medicine16th  Edition, Page 631; Excellent Care for Cancer Survivors: A Guide to Fully Meet Their Needs By Kenneth Miller – Pg 327; Childhood Leukemia: A Practical Handbook, By Gregory H. Reaman – Pg 11

 

Quiz In Between


Q. 4

All of the following are poor prognostic factors in a case of acute myeloid leukemias, except:

 A

Age more than 60 years

 B

Presence of t(8:21)

 C

Secondary leukemias

 D

Leucocyte count more than 1,00,000/microl

Q. 4

All of the following are poor prognostic factors in a case of acute myeloid leukemias, except:

 A

Age more than 60 years

 B

Presence of t(8:21)

 C

Secondary leukemias

 D

Leucocyte count more than 1,00,000/microl

Ans. B

Explanation:

Patients t(8;21) and inv(16) has a good prognosis, approximately 55% of these patients are cured. t(15:17) is associated with a very good prognosis, while those without any cytogenetic abnormality have a moderately favorable outcome.

 
Ref: Harrison’s Internal Medicine, 18th Edition, Chapter 109

Q. 5

Which of the following is a poor prognostic factor in Acute Myeloid Leukemia (AML)

 A

Monosomy

 B

Deletion of X or Y chromosome

 C

t (8; 21) translocation

 D

Nucleophosphin mutation

Q. 5

Which of the following is a poor prognostic factor in Acute Myeloid Leukemia (AML)

 A

Monosomy

 B

Deletion of X or Y chromosome

 C

t (8; 21) translocation

 D

Nucleophosphin mutation

Ans. A

Explanation:

Answer is A (Monosomy)

Monosomy is consistently associated with an unfavorable or poor prognosis.

Monosomy is associated with a poor prognosis

Monosomy especially those involving chromosome 7 (monosomy 7) and chromosome 5 (monosomy 5) are consistently associated with poor prognosis in both adults and children with AML

Deletion of X or Y chromosome is associated with a favorable / intermediate prognosis

‘Monosomy of the X chromosome in a female patient (loss of the Y chromosome) is the most common whole chromosome loss identified in pediatric patients with AML. This numeric abnormality is usually associated with t(8; 21) translocation and AML M2 which carry a good prognosis’ – ‘Childhood Leukemias’ by Puri 2″d/253

`Loss of Y and X chromosomes are most frequently observed in patients with t(8; 21) which carries a favourable prognosis’ – ‘Blood: Principles and Practice of Hematology’ 2″d/108

Nucleophosphin mutation is associated with a favorable prognosis

 

Factor

Favourable

Unfavourable

Nucleophosphin mutation

Present

Absent

t (8; 21) translocation is associated with a favorable prognosis

Factor

Favourable

Unfavourable

Cytogenetics

t(15;17),

1(8;21),

inv(16)

-7, del(7q),

-5, del(5q),

3q21 and 3q26 abnormalities, complex karyotypes

 

Prognostic Feature in Acute Myeloid Leukemia:

 

Factor                                                          Favourable                           Unfavourable

Clinical

Age

<45 yr

<2yr, >60yr

ECOG performance status

0-1

> I

Leukemia

De novo

Antecedent hematologic disorder,

myelodysplasia, myeloproliferative disorder

Infection

Absent

Present

Prior chemotherapy

No

Yes

Leukocytosis

<25,000/mm3

> 100,000/mm2

Serum LDH

Normal

Elevated

Extramedullary disease

Absent

Present

CNS disease

Absent

Present

Cytoreduction

Rapid

Delayed

Morphology

Auer rods

Present

Absent

Eosinophils

Present

Absent

Megaloblastic erythroids

Absent

Present

Dysplastic megakaryocytes

Absent

Present

FAB type

M2, M3, M4

MO, M6, M7

Surface/enzyme markers

Myeloid

CD34-, CDI4-, CD13-

CD34+

HLA-DR

Negative

Positive

TdT

Absent

Present

Lymphoid

Cd2+

CD7+, CD56+

Biphenotypic (2 or more lymphoid markers)

Present

MDR-1

Absent

Cytogenetics

Cytogenetics

1(15;17), 1(8;21), inv(16)

-7, del(7q), -5, del(5q), 3q21 and 3q26

abnormalities, complex karyotypes

 

 

Molecular markers

Fms-related tyrosine kinase-3 mutation

Absent

Present

Ecotropic viral integration site 1

expression

Absent

Present

Mixed-lineage leukemia partial tandem

duplication

Absent

Present

Nucleophosphin mutation

Present

Absent

CCAAT/enhancer-binding protein- a

mutation

Present

Absent

Brain and acute leukemia cytoplasmic

gene expression

Absent

Present

Vascular endothelial growth factor

expression

Absent

Present

 


Q. 6

In acute myeloid leukemia, Auer rods are numerous in:

September 2009

 A

M2

 B

M3

 C

M4

 D

M5

Q. 6

In acute myeloid leukemia, Auer rods are numerous in:

September 2009

 A

M2

 B

M3

 C

M4

 D

M5

Ans. B

Explanation:

Ans. B: M3

The diagnosis of AML is based on the presence of at least 20% myeloid blasts in the bone marrow. Myeloblast have delicate nuclear chromatin, two to four nucleoli, and more voluminous cytoplasm than lymphoblasts.

The cytoplasm often contains fine, peroxidase-positive azurophilic granules.

Auer rods, distinctive needle like azurophilic granules, are present in many cases; they are particularly numerous in AML with the t(15;17) (acute promyelocytic leukaemia-M3).

Quiz In Between



Acute myeloid leukemia (AML)

Acute myeloid leukemia (AML)


ACUTE MYELOID LEUKEMIA (AML)

  • AML is a heterogenous disease characterised by infiltration of malignant myeloid cells into blood, bone marrow.
  • AML is due to inhibition of maturation of myeloid stem cells due to mutations.
  • Seen in mainly in adults (50 years).
  • Chromosomal mutations in AML are
  1. translocation t (8: 21) & t (15: 17)
  2. Inversion  16 or t (16: 16)

Etiology-

  • Hereditary – Down syndrome, Klinefelter’s Syndrome, Patau Syndrome.
  • Radiation
  • Chemical- smoking

Pathogenesis-

  • t (8: 21) disrupt the RUNXL gene & Inv (16) disrupts the CDF1β gene both have good prognosis.
  • t (15: 17) (acute promyelocytic leukaemia-M3) have good prognosis.
  • Gene mutation encoding components of cohesion complex.
  • Most common congenital AML (in infants) are AML M5 (acute monocytic leukemia)
  • Most common AML in children is AML M7 (acute megakaryoblastic anaemia)
  • Most common translocation- MLL gene rearrangements on chromosome 11q.
  • Monosomy is associated with a poor prognosis. 

Clinical features-

1. Due to bone marrow failure-

  • Anaemia
  • Bruises, petechiae, bleeding from gum
  • Infection
  • Fever

2. Due to organ infiltration-

  • Pain & tenderness of bones
  • Lymphadenopathy, enlargement of tonsils
  • Splenomegaly
  • Hepatomegaly
  • Gum hypertrophy
  • Chloroma

Investigations-

1. Blood picture-

  • Anemia
  • Thrombocytopenia
  • WBC increased

2. Bone marrow examination

  • Cellularity- marrow is hypercellular but blood tap or dry tap is seen.
  • Leukemic cells- Blast cell count >20% (WHO)
  • Dyserythropoiesis, megaloblastic features & ring sideroblasts are common.
  • Megakaryocytes.

3. Cytochemistry-

  • Myeloperoxidase- Positive in immature myeloid cells containing granules & Auer rods (most definitive sign of myeloid differentiation)
  • Cluster of Auer rods called as Faggot.
  • Auer rods, distinctive needle like azurophilic granules,they are particularly numerous in AML with the t (15: 17) (acute promyelocytic leukaemia-M3).
  • Non specific esterase (NSE)- positive in monocytic series (M3, M4 & M5)
  • Investigation of choice is flow cytometry.

Treatment-

  • Blood transfusion & platelet transfusion.
  • Cytotoxic drug therapy- most effective treatment of AML is cytosine, arabinoside, anthracyclines.
  • Promyelocytic leukemia (M3)- tretinoin orally
  • Bone marrow transplantation.

Exam Important

  • AML is due to inhibition of maturation of myeloid stem cells due to mutations.
  • Seen in mainly in adults (50 years).
  • Chromosomal mutations in AML are
  1. translocation t (8: 21) & t (15: 17)
  2. Inversion  16 or t (16: 16)

Pathogenesis-

  • t (8: 21) disrupt the RUNXL gene
  • Inv (16) disrupts the CDF1β gene.
  • Gene mutation encoding components of cohesion complex.
  • Most common congenital AML (in infants) are AML M5 (acute monocytic leukemia)
  • Most common AML in children is AML M7 (acute megakaryoblastic anaemia)
  • Most common translocation- MLL gene rearrangements on chromosome 11q.

Investigations-

  • Leukemic cells- Blast cell count >20% (WHO)
  • Dyserythropoiesis, megaloblastic features & ring sideroblasts are common
  • Myeloperoxidase- Positive in immature myeloid cells containing granules & Auer rods (most definitive sign of myeloid differentiation)
  • Cluster of Auer rods called as Faggot.
  • Non specific esterase (NSE)- positive in monocytic series (M3, M4 & M5)
  • Investigation of choice is flow cytometry

Treatment-

  • Cytotoxic drug therapy- most effective treatment of AML is cytosine, arabinoside, anthracyclines.
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